gnomad-database

name

gnomad-database

description

Query the Genome Aggregation Database (gnomAD). Use when determining the rarity or allele frequency of specific genetic variants, retrieving gene constraint metrics (pLI, LOEUF) to assess loss-of-function intolerance, finding variants in a genomic region or gene, or querying structural variants. Don't use for analyzing individual patient genomes, tracking somatic mutations in cancer (use COSMIC), or requesting raw sequencing reads (use ENA).

gnomAD Database

Prerequisites

1. uv: Read the uv skill and follow its Setup instructions to ensure uv is installed and on PATH.
2. User Notification: If LICENSE_NOTIFICATION.txt does not already exist in this skill directory then (1) prominently notify the user to check the terms at https://gnomad.broadinstitute.org/policies and https://gnomad.broadinstitute.org/data#api, then (2) create the file recording the notification text and timestamp.

Core Rules

• Use the Wrapper: ALWAYS execute the provided helper scripts to query the database rather than accessing the database directly. The scripts automatically enforce the gnomAD API rate limits gracefully.
• Notification: If this skill is used, ensure this is mentioned in the output.

Utility Scripts

All scripts are located in the scripts/ subdirectory of this skill's installation directory. When running them, use the full absolute path to the script (e.g. /path/to/gnomad_database/scripts/get_variant_frequency.py).

1. Variant Frequency. Retrieves global and ancestry-specific allele frequencies, homozygote counts, and Grpmax Filtering AF (faf95/faf99) for exome, genome, and total (exome+genome combined) data. The filtering allele frequency (FAF) is the maximum credible genetic ancestry group AF (lower bound of the 95% or 99% CI). Variant ID format must be chrom-pos-ref-alt (e.g., 1-55516888-G-GA). Alternately, you may provide an rsID.

# By variant ID:
uv run scripts/get_variant_frequency.py --variant_id {variant_id} [--dataset {dataset}] --output variant_frequency.json

# By rsID (e.g., rs1800562):
uv run scripts/get_variant_frequency.py --rsid {rsid} [--dataset {dataset}] --output variant_frequency.json

2. Gene Constraint. Retrieves constraint metrics for a gene. The response will explicitly contain pli, and the LOEUF score is represented by oe_lof_upper.

uv run scripts/get_gene_constraint.py --gene {gene_symbol} --output {gene_symbol}_constraint.json

3. Region/Gene Variant Search. Finds all variants in a region or gene.

# By region:
uv run scripts/search_variants.py --chrom {chrom} --start {start} --end {end} --output region_variants.json
# By gene:
uv run scripts/search_variants.py --gene {gene_symbol} --consequence {pLoF|missense} --output {gene_symbol}_variants.json

References

Further documentation on the data: https://gnomad.broadinstitute.org/data#api More general database documentation: https://gnomad.broadinstitute.org/help