6b285a53b036b309e3c7a9b61d3741731088a172 lrnassar Fri Jun 12 02:35:01 2026 -0700 varFreqs: switch affectedAF/backgroundAF from max-across-cohorts to pooled sum(AC)/sum(AN) so the rate matches the carrier count scale. Per-arm AN is derived as round(AC/AF) when both are reported. An optional "default_an" column was added to databases.tsv so AF-only cohorts (ABraOM, ALFA) can synthesize a denominator from their cohort size; without it those cohorts had been silently dropped from the pooled rate. New affectedAN and backgroundAN columns expose the pool denominator. The mouseOver now reads "Affected AC/AN: 33238 / 213153" so the ratio is visible. Per-arm cohorts that ship only AC and no default_an (MGRB, GREGoR AC_AFFECTED/UNAFFECTED/UNKNOWN, AllOfUs per-population) are still listed in affectedCohorts/backgroundSources but contribute 0 to the pool, preserving the invariant pool_AF <= 1. The build pipeline is unchanged: re-run vcfToBigBed.py --split-affected against the existing merged.annotated.vcf.gz. refs #36642 diff --git src/hg/makeDb/trackDb/human/varFreqsBackground.html src/hg/makeDb/trackDb/human/varFreqsBackground.html index e835ddfe2a4..e63ca161efb 100644 --- src/hg/makeDb/trackDb/human/varFreqsBackground.html +++ src/hg/makeDb/trackDb/human/varFreqsBackground.html @@ -27,42 +27,60 @@ ColorConsequence classExamples   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. +The score (used for shading) is the pooled background allele frequency times 1000. +

+ +

Pooled allele frequency

+

+Background AF is the pooled rate across contributing population cohorts and +unaffected/control arms: backgroundAF = sum(AC) / sum(AN), where +backgroundAC sums the allele counts and backgroundAN sums the allele +numbers across each cohort/arm that ships both AC and AF (the per-arm AN is derived as +round(AC / AF)). Two cohorts that publish only AF (ABraOM, ALFA) contribute +via a configured default_an in the build configuration. Cohorts that publish +only AC with no default_an set (currently MGRB and the GREGoR unaffected and +unknown arms), and cohorts that contribute only through per-population AC/AF (currently +AllOfUs), are listed in backgroundSources but do not contribute to the pool +numerator or denominator; their data remain visible in the per-database and per-population +AC/AF columns. The pooled rate is preferred over a max-across-cohorts statistic so a small +cohort with a high local AF (for example AllOfUs Oceanian) cannot dominate the displayed +frequency.

Filters

Methods

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