JSON Output file
IAE produces an output file in JSON format that includes the following three sections:
|
Section |
Content |
|---|---|
|
Header |
Configuration, data source versions, and sample names. |
|
Positions |
Variant level annotation. |
|
Genes |
Gene level annotation. |
The following are outputs using the example commands specified in the sections above. Each of the following sections contains only a subset of information. The output file contains more information.
Header
The following is an example of the Header section.
"header": {
"annotator": "Nirvana 3.9.0",
"creationTime": "2020-06-03 08:05:06",
"genomeAssembly": "GRCh38",
"schemaVersion": 6,
"dataVersion": "91.26.57",
"dataSources": [
{
"name": "VEP",
"version": "91",
"description": "BothRefSeqAndEnsembl",
"releaseDate": "2018-03-05"
},
{
"name": "ClinVar",
"version": "20200302",
"description": "A freely accessible, public archive of reports of the relationships among human variations and phenotypes, with supporting evidence",
"releaseDate": "2020-03-02"
},
{
"name": "dbSNP",
"version": "153",
"description": "Identifiers for observed variants",
"releaseDate": "2019-07-22"
},
{
"name": "gnomAD",
"version": "2.1",
"description": "gnomAD allele frequency data remapped to GRCh38 with CrossMap by Ensembl",
"releaseDate": "2019-03-25"
},
{
"name": "PrimateAI",
"version": "0.2",
"description": "PrimateAI percentile scores.",
"releaseDate": "2018-11-07"
},
{
"name": "OMIM",
"version": "20200409",
"description": "An Online Catalog of Human Genes and Genetic Disorders",
"releaseDate": "2020-04-09"
}
],
"samples": [
"NA12878"
]
},
Positions
Each position represents one row of the VCF file. Each position contains a samples section and a variants section. Reference and alternate alleles shown here matches the VCF content exactly.
The samples section lists the sample-specific information, such as genotype, in the same order as they appear in the VCF and in the JSON header above.
The variants section provides annotations for each alternate allele that appear in the VCF row. This includes allele-specific annotation from external data sources as well as transcript-level annotation. Reference and alternate alleles shown here are shown in their most shortened representation. For example, padding bases have been removed and the variant are left-aligned.
"positions": [
{
"chromosome": "chr1",
"position": 1043248,
"refAllele": "C",
"altAlleles": [
"T"
],
"quality": 441.42,
"filters": [
"PASS"
],
"strandBias": -425.94,
"cytogeneticBand": "1p36.33",
"samples": [
{
"genotype": "0/1",
"variantFrequencies": [
0.537
],
"totalDepth": 54,
"genotypeQuality": 99,
"alleleDepths": [
25,
29
]
}
],
"variants": [
{
"vid": "1-1043248-C-T",
"chromosome": "chr1",
"begin": 1043248,
"end": 1043248,
"refAllele": "C",
"altAllele": "T",
"variantType": "SNV",
"hgvsg": "NC_000001.11:g.1043248C>T",
"phylopScore": 0.1,
"clinvar": [
{
"id": "RCV000872112.1",
"variationId": 263161,
"reviewStatus": "criteria provided, single submitter",
"alleleOrigins": [
"germline"
],
"refAllele": "C",
"altAllele": "T",
"phenotypes": [
"not provided"
],
"medGenIds": [
"CN517202"
],
"significance": [
"likely benign"
],
"lastUpdatedDate": "2019-12-17",
"pubMedIds": [
"28492532"
],
"isAlleleSpecific": true
},
{
"id": "VCV000263161.2",
"reviewStatus": "criteria provided, multiple submitters, no conflicts",
"significance": [
"likely benign"
],
"refAllele": "C",
"altAllele": "T",
"lastUpdatedDate": "2019-12-17",
"isAlleleSpecific": true
}
],
"dbsnp": [
"rs116586548"
],
"globalAllele": {
"globalMinorAllele": "T",
"globalMinorAlleleFrequency": 0.004393
},
"gnomad": {
"coverage": 38,
"allAf": 0.000681,
"allAn": 264462,
"allAc": 180,
"allHc": 0,
"afrAf": 0.006216,
"afrAn": 23648,
"afrAc": 147,
"afrHc": 0,
"amrAf": 0.000689,
"amrAn": 33404,
"amrAc": 23,
"amrHc": 0,
"easAf": 0,
"easAn": 18830,
"easAc": 0,
"easHc": 0,
"finAf": 0,
"finAn": 22870,
"finAc": 0,
"finHc": 0,
"nfeAf": 5e-05,
"nfeAn": 120576,
"nfeAc": 6,
"nfeHc": 0,
"asjAf": 0.000304,
"asjAn": 9882,
"asjAc": 3,
"asjHc": 0,
"sasAf": 0,
"sasAn": 28456,
"sasAc": 0,
"sasHc": 0,
"othAf": 0.000147,
"othAn": 6796,
"othAc": 1,
"othHc": 0,
"maleAf": 0.000564,
"maleAn": 143614,
"maleAc": 81,
"maleHc": 0,
"femaleAf": 0.000819,
"femaleAn": 120848,
"femaleAc": 99,
"femaleHc": 0,
"controlsAllAf": 0.000626,
"controlsAllAn": 113456,
"controlsAllAc": 71
},
"oneKg": {
"allAf": 0.004393,
"afrAf": 0.016641,
"amrAf": 0,
"easAf": 0,
"eurAf": 0,
"sasAf": 0,
"allAn": 5008,
"afrAn": 1322,
"amrAn": 694,
"easAn": 1008,
"eurAn": 1006,
"sasAn": 978,
"allAc": 22,
"afrAc": 22,
"amrAc": 0,
"easAc": 0,
"eurAc": 0,
"sasAc": 0
},
"primateAI": [
{
"hgnc": "AGRN",
"scorePercentile": 0.12
}
],
"revel": {
"score": 0.136
},
"spliceAI": [
{
"hgnc": "AGRN",
"acceptorGainScore": 0.1,
"acceptorGainDistance": 23,
"acceptorLossScore": 0,
"acceptorLossDistance": -9,
"donorGainScore": 0,
"donorGainDistance": -5,
"donorLossScore": 0,
"donorLossDistance": 16
}
],
"topmed": {
"allAf": 0.002055,
"allAn": 125568,
"allAc": 258,
"allHc": 1
},
"transcripts": [
{
"transcript": "ENST00000379370.6",
"source": "Ensembl",
"bioType": "protein_coding",
"codons": "cCg/cTg",
"aminoAcids": "P/L",
"cdnaPos": "1444",
"cdsPos": "1394",
"exons": "8/36",
"proteinPos": "465",
"geneId": "ENSG00000188157",
"hgnc": "AGRN",
"consequence": [
"missense_variant"
],
"hgvsc": "ENST00000379370.6:c.1394C>T",
"hgvsp": "ENSP00000368678.2:p.(Pro465Leu)",
"isCanonical": true,
"polyPhenScore": 0.065,
"polyPhenPrediction": "benign",
"proteinId": "ENSP00000368678.2",
"siftScore": 0.05,
"siftPrediction": "tolerated"
},
{
"transcript": "NM_198576.3",
"source": "RefSeq",
"bioType": "protein_coding",
"codons": "cCg/cTg",
"aminoAcids": "P/L",
"cdnaPos": "1444",
"cdsPos": "1394",
"exons": "8/36",
"proteinPos": "465",
"geneId": "375790",
"hgnc": "AGRN",
"consequence": [
"missense_variant"
],
"hgvsc": "NM_198576.3:c.1394C>T",
"hgvsp": "NP_940978.2:p.(Pro465Leu)",
"isCanonical": true,
"polyPhenScore": 0.065,
"polyPhenPrediction": "benign",
"proteinId": "NP_940978.2",
"siftScore": 0.05,
"siftPrediction": "tolerated"
}
]
}
]
}
],
Genes
For each gene referenced in the transcripts in the positions section, there is a matching entry in the genes section. The following example shows gene-level annotations from gnomAD, ClinGen Dosage Sensitivity Map, and OMIM.
"genes": [
{
"name": "AGRN",
"gnomAD": {
"pLi": 5.47e-07,
"pRec": 1,
"pNull": 1.41e-12,
"synZ": -3.96,
"misZ": 0.226,
"loeuf": 0.435
},
"clingenDosageSensitivityMap": {
"haploinsufficiency": "gene associated with autosomal recessive phenotype",
"triplosensitivity": "no evidence to suggest that dosage sensitivity is associated with clinical phenotype"
},
"omim": [
{
"mimNumber": 103320,
"geneName": "Agrin",
"description": "The AGRN gene encodes agrin, a large and ubiquitous proteoglycan with multiple isoforms that have diverse functions in different tissues. Agrin was originally identified as an essential neural regulator that induces the aggregation of acetylcholine receptors (AChRs) and other postsynaptic proteins on muscle fibers and is crucial for the formation and maintenance of the neuromuscular junction (NMJ) (Campanelli et al., 1991; Burgess et al., 1999; summary by Maselli et al., 2012).",
"phenotypes": [
{
"mimNumber": 615120,
"phenotype": "Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects",
"description": "Congenital myasthenic syndromes are genetic disorders of the neuromuscular junction (NMJ) that are classified by the site of the transmission defect: presynaptic, synaptic, and postsynaptic. CMS8 is an autosomal recessive disorder characterized by prominent defects of both the pre- and postsynaptic regions. Affected individuals have onset of muscle weakness in early childhood; the severity of the weakness and muscles affected is variable (summary by Maselli et al., 2012).\n\nFor a discussion of genetic heterogeneity of CMS, see CMS1A.",
"mapping": "molecular basis of the disorder is known",
"inheritances": [
"Autosomal recessive"
]
}
]
}
]
}
]
}
