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