+This track shows small variants (SNVs and short indels) seen in population reference +cohorts and in unaffected or control individuals of disease-study cohorts, annotated +with their predicted protein consequence and colored by severity. It is the background half +of a matched pair: the companion +Affected/Case Individuals track shows the same +kind of variants seen in affected or case individuals. Displaying the two together lets you +see how common a variant is in the general/unaffected population compared with affected +individuals. For the full list of contributing projects, see the +SNV Frequencies collection page. +
++The background combines two kinds of data: the population/biobank reference cohorts (such as +gnomAD HGDP+1kG, TOPMed, ALFA, HRC and the many national WGS projects), and the +unaffected/control or unknown-phenotype arms of the disease-study cohorts (non-ASD family +members in SFARI SPARK WES/WGS, SCHEMA controls, and GREGoR unaffected/unknown +participants). Genotyping-array cohorts are not included. A variant that also appears in +affected individuals is shown in both this track and the +Affected/Case Individuals track. +
+ +Variants are colored by their most severe predicted consequence:
+| Color | Consequence class | Examples |
|---|---|---|
| + | Protein-truncating / loss-of-function | +stop_gained, frameshift, splice_donor, splice_acceptor, stop_lost, start_lost |
| + | Missense / in-frame | +missense, inframe_insertion, inframe_deletion, protein_altering |
| + | Synonymous | +synonymous, stop_retained |
| + | Non-coding / intergenic | +intron, non_coding, intergenic, UTR |
+The score (used for shading) is the background allele frequency (the maximum across the +population cohorts and unaffected/control arms) times 1000. +
+ +
+Variant-frequency VCFs from the contributing cohorts were stripped of unneeded INFO fields,
+normalized with bcftools norm (splitting multi-allelic sites), and merged with
+bcftools merge. The merged callset was annotated with predicted protein
+consequences using bcftools csq against the
+Ensembl
+GRCh38 release 115 gene models.
+
+A custom Python script (vcfToBigBed.py) then read the per-cohort allele
+frequencies and, for each variant, summed/maximized the counts across the population cohorts
+and unaffected/control subgroups to produce this track, and across the affected arms to
+produce the companion
+Affected/Case Individuals track. A variant seen
+in both groups appears in both tracks. The build is documented in the
+makeDoc, and the scripts are on
+GitHub.
+
+Because the merged callset combines cohorts whose redistribution licenses differ, this +track is not available for download and is not in the Table Browser. It can be +reconstructed from the individual source VCFs using the +conversion scripts and the +build documentation. The per-project subtracks on the +SNV Frequencies collection page document how to obtain +each source dataset. +
+ ++This track is only possible thanks to the data from millions of volunteers around the world +who contributed to the population reference projects and to the unaffected/control arms of +the disease cohorts. Click the individual project subtracks on the +SNV Frequencies collection page for the specific credits +and citations of each cohort. Thanks to Alex Ioannidis, UCSC, for the inspiration for this +track and to Andreas Lahner, MGZ, for feedback. +
+ ++For the primary citation of each source cohort, see the References section on the +SNV Frequencies collection page. The merged-track build +uses the following tools: +
++Danecek P, McCarthy SA. + +BCFtools/csq: haplotype-aware variant consequences. +Bioinformatics. 2017 Jul 1;33(13):2037-2039. +PMID: 28205675; +PMC: PMC5870570 +