gnomad-database

这段内容是审核时保存的快照。外部来源才是完整且最新的版本。

---
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 .licenses/gnomad_database_LICENSE.txt does not
    already exist in the workspace root 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`.

```bash
# 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`.

```bash
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.

```bash
# 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