Variant Filters

The following table lists the variant grid filters.

Filter

Description

Variant Category

Filters by variant category.

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Small Variant—SNVs, MNVs, insertions, deletions, and indels.

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Structural Variant—Insertions, deletions, tandem duplications, and translocation breakends.

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Copy Number Variant—Copy number variation, gain, or loss.

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Run of Homozygosity—Regions of consecutive variant calls.

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Short Tandem Repeats—Regions of repeating short DNA segments.

AI Prediction Engine

Filters data by splice mutation probability, as predicted by deep learning engines.

Chromosome

Filters by specified chromosomes. If no chromosome is selected, the chromosome filter is not applied.

Constraint Metrics (gnomAd)

Filters by gnomAD constraint metrics.

Copy Number Variant Consequences

Filters data by copy number variant consequences. See Copy Number Variant Consequence Filters.

Copy Number Variant Type

Filters by copy number variant type.

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Copy Number Variation—The copy number is increased or decreased relative to the reference sequence.

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Copy Number Loss—The copy number is less than the reference sequence.

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Copy Number Gain—The copy number is greater than the reference sequence.

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Copy Number Neutral—The copy number is the same as the reference sequence.

[Custom Annotation Filter]

Filters by data provided in a custom annotation file. The filter name corresponds to the filter annotation label.

For more information, see Custom Annotation Files.

[Custom Annotation Score]

Filters by data provided in a custom annotation file. The filter name corresponds to the score annotation label. For more information, see Custom Annotation Files.

Emedgene

Filters by the predicted probability that the variant is causative.

Flags

Filters variants applied a flag by a user.

Genes

Filters by specified genes and genes related to specified phenotypes. Gene names are case-sensitive.

Genetic Findings

Filters by the status of the SMN and STR calls for each sample.

Genomic Regions

Filters by specified regions.

The input format is chr#:start-end, with multiple regions separated by spaces or new lines.

Haploinsufficiency (ClinGen)

Filters by the ClinGen haploinsufficiency evidence classification.

Inherited From

Filters variants by the computed inheritance of a variant.

Low Complexity Region (gnomAD)

Excludes small variants in low complexity regions (LCRs).

Mitochondrial Heteroplasmy

Filters data by the positive difference in Variant Read Frequency between proband and mother.

Mitochondrial variants are typically maternally inherited, though the variant read frequency can differ between parent and proband. An increase in variant read frequency for a pathogenic mitochondrial variant might result in mitochondrial disorder.

The input value range is 0–1, with precision to 0.0001.

Mode of Inheritance

Filters data by the mode of inheritance. Selecting an inheritance option enables one or more subfilters to select from.

For filter options, see Mode of Inheritance Filters.

For information about inheritance criteria, see Mode of Inheritance Logic .

OMIM

Filters data by presence in the OMIM gene database.

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Present in OMIM—An OMIM entry exists for the gene.

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Has associated OMIM phenotypes (including ?)—A relationship exists between the phenotype and a matching gene at the transcript level. Provisional relationships, indicated by "?" in OMIM, are included.

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Has associated OMIM phenotypes (excluding ?)—A relationship exists between the phenotype and a matching gene at the transcript level. Provisional relationships, indicated by "?" in OMIM, are excluded.

Selecting associated phenotypes enables options to refine the filter by mode of inheritance. For a description of the inheritance options, see OMIM Mode of Inheritance Filters.

Pathogenicity

Filters data by pathogenic evidence. For filter options, see Pathogenicity Filters.

Population Frequency

Filters data based on the allele frequency in population studies and custom annotation data. Large variants (eg, CNVs and SVs) are filtered based on aggregate frequency. Aggregate frequency is calculated as the sum of all allele frequencies for annotations where the number of alleles is at least 300 and the reciprocal overlap is above the threshold set in the test definition.

The available population databases vary depending on the selected variant type. For more information, see Population Data.

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To set a variant filter for frequency values, enter a value from 0–1 in the field. Frequency values support precision to 0.00001.

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To filter by the average frequency across all options in a database, enter a value in the All Populations field.

QC Regions.Callability

Filters data by the percent callability reported in the exome analysis QC coverage BED file. For more information, see Test Parameters .

QC Regions.Max Coverage

Filters data by the maximum coverage value reported in the exome analysis QC coverage BED file. For more information, see Test Parameters .

QC Regions.Mean Coverage

Filters data by the mean coverage value reported in the exome analysis QC coverage BED file. For more information, see Test Parameters .

QC Regions.Median Coverage

Filters data by the median coverage value reported in the exome analysis QC coverage BED file. For more information, see Test Parameters .

QC Regions.Min Coverage

Filters data by the minimum coverage value reported in the exome analysis QC coverage BED file. For more information, see Test Parameters .

QC Regions.Total Coverage

Filters data by the total coverage value reported in the exome analysis QC coverage BED file. For more information, see Test Parameters .

Quality

Filters data by whether variants pass filter.

Sample Metrics

Filters data by read metrics.

Size

Filters data by variant length. Supports decimal values for sizes < 1 Mbp, with precision to 0.001.

Short Tandem Repeat Consequences

Filters data by short tandem repeat consequences: expansion, contraction, and change.

Small Variant Consequences

Filters data by small variant consequences. See Small Variant Consequence Filters.

Small Variant Type

Filters data by small variant type.

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SNV—Single nucleotide variation.

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MNV—Multiple nucleotide variation.

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Insertion—Insertion of genomic sequence.

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Deletion—Deletion of a genomic sequence.

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Indel—Deletion and insertion of genomic sequence.

Structural Variant Consequences

Filters data by structural variant consequences. See Structural Variant Consequence Filters.

Structural Variant Type

Filters data by structural variant type.

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Insertion—Insertion of genomic sequence.

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Deletion—Deletion of a genomic sequence.

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Tandem duplication—Duplication of genomic sequence in tandem.

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Translocation breakend—Structural variation that links breakpoints of two different points in the genome.

Triplosensitivity (ClinGen)

Filters by the ClinGen triplosensitivity classification.

Zygosity

Filters by zygosity. Subjects with unknown affected status are considered neither affected nor unaffected, and are omitted from zygosity filters that are configured by tests.

Present

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Homozygous—Variants that are present on both alleles.

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Heterozygous—Variants that are present on one of two alleles.

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Hemizygous Diploid Loss—Variants that are present on one allele, where the other allele is deleted due to a copy number variation.

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Hemizygous— Variants that are present on one allele for nondiploid regions.

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Homoplasmic— Variants observed at ≥ 95% frequency in mtDNA.

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Heteroplasmic— Variants that are observed at < 95% frequency in mtDNA.

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Observed— A call that is not applicable to any of the other categories (eg, ROH and SMN1).

Not Present

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Reference—Variants that match the reference genome.

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Non-Reference— Variants that do not match the reference genome.

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Not Observed— An observed call that is present for other individuals is absent for this individual.

Small Variant Consequence Filters

When annotating transcripts with terms from Sequence Ontology, TruSight Software uses the most specific term supported by the variant annotator.

Consequence filters return only the specified term and do not automatically include child terms. Specify the exact terms to include them in filter results.

Coding Consequences

Start and Stop Alterations

Filters data by the presence and location of start and stop alterations.

Consequence	Description
Start Loss	The loss of a start codon in the coding sequence.
Stop Gained	The gain of a stop codon in the coding sequence.
Stop Loss	The loss of a stop codon in the coding sequence.
Incomplete Terminal Codon	A change to at least one base of the final codon of an incomplete annotated transcript.
Feature Elongation	The variant causes the extension of a genomic feature.
Feature Truncation	The variant causes the reduction of a genomic feature.

Splice Site

Filters data by the affected splice site.

Type	Description
Splice Acceptor Variant	The variant affects the canonical splice acceptor site (last two bases of the 3ʹ end of the intron).
Splice Donor Variant	The variant affects the canonical splice donor site (first two bases of the 5ʹ end of the intron).
Splice Region Variant	An indel or substitution in a noncoding splice region of the gene.

Indels

Type	Description
Frameshift Variant	An insertion or deletion in which the number of base pairs is not divisible by 3, causing a frame disruption.
Inframe Deletion	A deletion that does not disrupt the reading frame.
Inframe Insertion	An insertion that does not disrupt the reading frame.

Other

Type	Description
Missense Variant	A single base pair substitution that results in the translation of a different amino acid at that position.
Protein Altering Variant	The variant has a protein-altering coding consequence.
Coding Sequence Variant	The variant changes the coding sequence.

Silent Consequences

Filters data by the variant relationship to a gene.

Type	Description
Intergenic Variant	The variant position is not covered by any gene transcript.
Upstream Gene Variant	The variant position is within 5 kb upstream of the defined transcript start coordinate.
Downstream Gene Variant	The variant position is within 5 kb downstream of the defined transcript end coordinate.
Intron Variant	The variant occurs within an intron region.
3-prime UTR Variant	The variant is in the 3ʹ untranslated region of a gene.
5-prime UTR Variant	The variant is in the 5ʹ untranslated region of a gene.
Noncoding Transcript Exon Variant	The variant changes the noncoding exon sequence in a noncoding transcript.
Noncoding Transcript Variant	The variant occurs in a noncoding RNA gene.
Synonymous Variant	The variant does not affect the primary amino acid sequence of the translated protein.
Start Retained Variant	At least one base in the start codon is changed, but the start codon remains.
Stop Retained Variant	At least one base in the terminator codon is changed, but the terminator remains.
Mature MiRNA Variant	The variant occurs within a mature miRNA sequence.
NMD Transcript Variant	The variant is in a transcript and is the target of nonsense‑mediated decay (NMD).
Regulatory Region Ablation	A deletion of a region that contains a regulatory region.
Regulatory Region Amplification	An amplification of a region that contains a regulatory region.
Regulatory Region Variation	The variant occurs in a regulatory region.

Structural Variant Consequence Filters

When annotating transcripts with terms from Sequence Ontology, TruSight Software uses the most specific term supported by the variant annotator.

Consequence filters return only the specified term and do not automatically include child terms. Specify the exact terms to include them in filter results.

Transcript Consequences

Filters data by the transcript consequence.

Consequence	Description
Transcript Variant	The variant changes the structure of the transcript.
Intron Variant	The variant is completely within the intron region of the gene.
Exon Variant	The variant is completely within the exon region of the gene.
Transcript Ablation	A deletion of a region that contains a transcript feature.
Transcript Amplification	An amplification of a region that contains a transcript.
Feature Elongation	The variant causes the extension of a genomic feature.
Feature Truncation	The variant causes the reduction of a genomic feature.
5-Prime Duplicated Transcript	A partially duplicated transcript in which the 5ʹ end of the transcript is duplicated.
3-Prime Duplicated Transcript	A partially duplicated transcript in which the 3ʹ end of the transcript is duplicated.

Gene Fusion Consequence

Filters data by the gene fusion consequence.

Consequence	Description
Unidirectional Gene Fusion	A fusion of two genes on the same strand.

Copy Number Variant Consequence Filters

When annotating transcripts with terms from Sequence Ontology, TruSight Software uses the most specific term supported by the variant annotator.

Consequence filters return only the specified term and do not automatically include child terms. Specify the exact terms to include them in filter results.

Transcript Consequences

Filters data by the transcript consequence.

Consequence	Description
Transcript Variant	The variant changes the structure of the transcript.
Intron Variant	The variant is completely within the intron region of the gene.
Exon Variant	The variant is completely within the exon region of the gene.
Transcript Ablation	A deletion of a region that contains a transcript feature.
Transcript Amplification	An amplification of a region that contains a transcript.
Transcript Truncation	A truncation of a region that contains a transcript.
Feature Elongation	The variant causes the extension of a genomic feature.
Feature Truncation	The variant causes the reduction of a genomic feature.
5-Prime Duplicated Transcript	A partially duplicated transcript in which the 5ʹ end of the transcript is duplicated.
3-Prime Duplicated Transcript	A partially duplicated transcript in which the 3ʹ end of the transcript is duplicated.

Copy Number Consequences

Filters data by the copy number consequence.

Type	Description
Copy Number Increase	The copy number is increased relative to the reference sequence.
Copy Number Decrease	The copy number is decreased relative to the reference sequence.
Copy Number Change	The copy number is increased or decreased.
Intron	The variant is completely within the intron region of the gene.
Exon	The variant is completely within the exon region of the gene.

OMIM Mode of Inheritance Filters

OMIM Mode of Inheritance	Description
AD	Autosomal dominant
AR	Autosomal recessive
XL	X-linked
XLD	X-linked dominant
XLR	X-linked recessive
YL	Y-linked
Mi	Mitochondrial
Mu	Multifactorial
DD	Digenic dominant
DR	Digenic recessive
SMu	Somatic mutation
SMo	Somatic mosaicism
IC	Isolated cases

Mode of Inheritance Filters

Selecting an inheritance option enables one or more subfilters to select from. Subjects with unknown affected status are considered neither affected nor unaffected, and are omitted from inheritance calculations and filters.

Mode of Inheritance

Description

De Novo (DN)

The variant is not present in the parents.

Dominant (DOM)

At least one parent is affected and the variant is present in all affected subjects.

Present in Proband (PR)

The variant is present in the proband subject.

Recessive (RSG or RCH)

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The variant is present in all affected individuals and is homozygous or hemizygous in the proband (RSG).

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The variant is heterozygous or hemizygous diploid loss in the proband (RCH).

Inheritance Subfilters

Filter	Description
Assume Complete Penetrance	Excludes variants that are homozygous or hemizygous in unaffected individuals. This option is used to find variants for which complete penetrance is expected.
Exclude Ambiguous	Excludes RCH variants that have ambiguous inheritance, if de novo variants are absent or have been filtered out.
Exclude Low Confidence	Excludes de novo variants that are classified as low confidence.
Exclude Observed Homozygotes	Excludes variants observed in a homozygous state within the pedigree.
In Affected	Excludes variants that are not present in all affected individuals.
Not in Unaffected	Excludes variants that are present in unaffected individuals.
Same Genotype in Affected	Returns variants that are homozygous, hemizygous, or hemizygous diploid loss in all affected individuals.
Shared Variant in Affected	Returns RSG variants that are present in all affected individuals or RCH variants where at least one variant from a given variant set for a transcript is present in all affected individuals.
Strict	Returns only recessive variants that are inherited from both parents.

Pathogenicity Filters

Filters data by the pathogenic evidence from ClinVar or your knowledge base.

Inclusion and exclusion filters capture all variants that have associations for the selected pathogenicity, regardless of any other pathogenicities associated with the variant. For example, a filter that excludes benign pathogenicities also excludes any variants that have both benign and pathogenic associations.

Pathogenicity	Description
P (Pathogenic)	Segregates with disease in multiple unrelated cases with control data. The variant is in a highly conserved region. Functional studies or other evidence indicate a deleterious effect on gene expression.
LP (Likely Pathogenic)	Reported in some case studies with or without control data. The variant is in a highly conserved region. Functional studies or other evidence highly suggest a deleterious effect on gene expression.
VUS (Variant of Uncertain Significance)	Nothing about this variant has been reported, or reported information is incomplete or contradictory.
LB (Likely Benign)	Functionally normal. Reported in a few cases with little or no control data. The variant might be nonconserved and predicted to be tolerated. Based on disease prevalence and penetrance information, the variant frequency is higher than expected in the general population.
B (Benign)	Functionally normal. Reported at high frequency in control data and does not segregate with disease. The variant might be nonconserved and predicted to be tolerated.

ClinVar Review Status

Filters selected ClinVar pathogenicities by review status.

# of Stars	Description
1	Single submitter or multiple submitters with conflicting evidence.
2	Multiple submitters, no conflicting evidence.
3	Reviewed by expert panel.
4	Practice guideline.