usage-guide.md

gnomAD Frequencies - Usage Guide

Overview

Query gnomAD (Genome Aggregation Database) to retrieve population allele frequencies for assessing variant rarity in rare disease analysis.

Prerequisites

pip install requests myvariant pandas

Quick Start

Tell your AI agent:

• "Get gnomAD frequency for this variant"
• "Filter my variants to keep only those with AF < 0.01"
• "Check if this variant is present in gnomAD"
• "Get population-specific frequencies from gnomAD"

Example Prompts

Single Variant Queries

"What is the gnomAD allele frequency for chr7-140453136-A-T?"

"Is rs121913527 rare in the general population?"

"Check gnomAD exome and genome frequencies for BRAF V600E"

Population-Specific

"Get gnomAD frequencies by ancestry for this variant"

"What is the East Asian frequency for this variant in gnomAD?"

"Compare European vs African frequencies for my variants"

Filtering

"Filter my VCF to variants with gnomAD AF < 0.001"

"Keep only variants absent from gnomAD"

"Find variants rare in Europeans but common in Africans"

What the Agent Will Do

1. Format variant identifier for gnomAD query
2. Query gnomAD API or myvariant.info
3. Extract exome and genome frequencies
4. Optionally retrieve population-specific frequencies
5. Apply filtering thresholds if requested

Tips

• Use both exome and genome - take the max AF for conservative filtering
• gnomAD v4 is the latest release with most samples (~800K exomes)
• Population stratification - some variants are common in one population but rare globally
• Absent != pathogenic - many benign variants are also rare
• ACMG PM2 uses AF < 0.01 (1%) as supporting evidence for pathogenicity