+This track merges variants from three genotyping-array cohorts into a single bigBed file +with predicted protein consequences and cross-database filtering. It contains 14.7 million +variants from the Taiwan Precision Medicine Initiative (TPMI Axiom TPM1 chip, +~1 million Han Chinese), the Mexico Biobank (MexBB, 6,011 individuals), and UK Biobank +(361k unrelated white British, imputed from the Neale Lab Round 2 release). +
+ ++The array track is kept separate from the +All Databases Combined WGS/WES summary so that +sequencing-based and array-based frequencies can be inspected independently. For a summary +of all available variant frequency databases, see the +SNV Frequencies supertrack page. +
+ +Variants are colored by their most severe predicted consequence:
+| Color | Consequence class | Examples |
|---|---|---|
| Red | +Protein-truncating / Loss-of-function | +stop_gained, frameshift, splice_donor, splice_acceptor, stop_lost, start_lost | +
| Blue | +Missense / In-frame | +missense, inframe_insertion, inframe_deletion, protein_altering | +
| Green | +Synonymous | +synonymous, stop_retained | +
| Grey | +Non-coding / Intergenic | +intron, non_coding, intergenic, UTR | +
+The "AA change" field uses bcftools csq notation: 23I>23V means position +23 changed from Isoleucine (I) to Valine (V) (missense). 23I alone (no arrow) +means position 23 is Isoleucine and unchanged (synonymous). A "*" indicates a +stop codon (e.g. 45R>45* is a stop_gained). +
+ ++Allele frequencies from genotyping arrays are not directly comparable to those from +whole-genome or whole-exome sequencing. Two limitations to keep in mind: +
+NGS_concordance value (chip-vs-sequencing concordance from
+ its own validation) in the source VCF; high-AF claims with low concordance are
+ common. MexBB ships only AN/AF/AC with no FILTER column and no per-site QC at all.
+ For both arrays, high-AF rare-disease candidates should be cross-checked against the
+ sequencing-based All Databases Combined track
+ before drawing conclusions.+This track supports filtering via the track settings page. Click the track title or use the +"Configure" button to access filters. +
+ ++The Source Database filter restricts the display to variants present in specific +databases. It uses OR logic. +
+ +
+The same merge-and-annotate pipeline used for the
+All Databases Combined track was run on the
+array-cohort subset of source VCFs. Each VCF was stripped of its INFO fields, normalized
+with bcftools norm (splitting multi-allelic sites), and merged with
+bcftools merge. The merged VCF was then annotated with predicted protein
+consequences using bcftools csq with the
+Ensembl
+GRCh38 release 115 gene annotation (GFF3).
+
+The track's +makeDoc file documents how each source VCF was converted. Scripts are +available from +Github. +
+ ++The data can be explored interactively with the +Table Browser or the +Data Integrator. For programmatic access, our +REST API can be used; the track +name is varFreqsArray. +
++Because the merged callset includes data from multiple sources whose redistribution +licenses differ, the combined bigBed is not available for download from our download +server. The combined track can be reconstructed from the individual source VCFs using the +conversion scripts on GitHub together with the +build documentation. +
+ ++This track is only possible thanks to the participants in TPMI, the Mexico Biobank, and UK +Biobank, who donated samples and provided health information. Click on the individual +TPMI, MexBB, or UK Biobank subtracks in the +SNV Frequencies supertrack for full project credits. +Thanks to Alex Ioannidis, UCSC, for the motivation for this track family and to Andreas +Lahner, MGZ, for feedback. +
+ ++For primary citations of each source dataset, see the References section on the +SNV Frequencies supertrack page. The merged-track +build itself 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 +
++McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GR, Thormann A, Flicek P, Cunningham F. + +The Ensembl Variant Effect Predictor. +Genome Biol. 2016 Jun 6;17(1):122. +PMID: 27268795; PMC: PMC4893825 +