gnomad-database

gnomAD Database

Overview

The Genome Aggregation Database (gnomAD) is the largest publicly available collection of human genetic variation, aggregated from large-scale sequencing projects. gnomAD v4 contains exome sequences from 730,947 individuals and genome sequences from 76,215 individuals across diverse ancestries. It provides population allele frequencies, variant consequence annotations, and gene-level constraint metrics that are essential for interpreting the clinical significance of genetic variants.

Key resources:

• gnomAD browser: https://gnomad.broadinstitute.org/
• GraphQL API: https://gnomad.broadinstitute.org/api
• Data downloads: https://gnomad.broadinstitute.org/downloads
• Documentation: https://gnomad.broadinstitute.org/help

When to Use This Skill

Use gnomAD when:

• Variant frequency lookup: Checking if a variant is rare, common, or absent in the general population
• Pathogenicity assessment: Rare variants (MAF < 1%) are candidates for disease causation; gnomAD helps filter benign common variants
• Loss-of-function intolerance: Using pLI and LOEUF scores to assess whether a gene tolerates protein-truncating variants
• Population-stratified frequencies: Comparing allele frequencies across ancestries (African/African American, Admixed American, Ashkenazi Jewish, East Asian, Finnish, Middle Eastern, Non-Finnish European, South Asian)
• ClinVar/ACMG variant classification: gnomAD frequency data feeds into BA1/BS1 evidence codes for variant classification
• Constraint analysis: Identifying genes depleted of missense or loss-of-function variation (z-scores, pLI, LOEUF)

Core Capabilities

1. gnomAD GraphQL API

gnomAD uses a GraphQL API accessible at https://gnomad.broadinstitute.org/api. Most queries fetch variants by gene or specific genomic position.

Datasets available:

• gnomad_r4 — gnomAD v4 exomes (recommended default, GRCh38)
• gnomad_r4_genomes — gnomAD v4 genomes (GRCh38)
• gnomad_r3 — gnomAD v3 genomes (GRCh38)
• gnomad_r2_1 — gnomAD v2 exomes (GRCh37)