SnpEff

Overview

SnpEff is a fast variant annotation and functional effect prediction tool that classifies genetic variants by their impact on known genes and proteins. Given a VCF file and a genome database, SnpEff reports the affected gene, transcript, exon or intron location, amino acid change, and predicted impact category (HIGH, MODERATE, LOW, or MODIFIER) for each variant. It bundles pre-built annotation databases for thousands of genomes and can annotate a whole-genome VCF in minutes. SnpEff is often used together with SnpSift, which provides utilities for filtering and extracting fields from annotated VCFs.

Installation

mamba install -c bioconda snpsift

This installs both SnpEff and SnpSift.

Basic Usage

Download the annotation database

snpEff download GRCh38.105

Annotate variants

snpEff ann GRCh38.105 variants.vcf.gz > annotated.vcf

The annotation is added to the INFO field of each VCF record as an ANN tag containing pipe-delimited fields for allele, effect, impact, gene name, gene ID, feature type, transcript ID, biotype, and HGVS notation.

Key Parameters

Flag / option	Description
`ann`	Annotate variants (primary sub-command).
`download`	Download a pre-built annotation database by name.
`-v`	Verbose output for logging and debugging.
`-canon`	Report annotations only for canonical transcripts.
`-noStats`	Skip generation of the HTML summary statistics file.
`-csvStats`	Write statistics in CSV format instead of HTML.
`-no-downstream`	Do not annotate downstream gene variants.
`-no-upstream`	Do not annotate upstream gene variants.
`-no-intergenic`	Do not annotate intergenic variants.
`-dataDir`	Path to the directory containing SnpEff databases.

Expected Output

Standard output – an annotated VCF with ANN fields in the INFO column describing the predicted effect of each variant on overlapping genes and transcripts. Each annotation includes: allele, annotation type (e.g. missense_variant, stop_gained), putative impact (HIGH/MODERATE/LOW/MODIFIER), gene name, gene ID, feature type, feature ID, transcript biotype, rank, HGVS.c, HGVS.p, cDNA position, CDS position, and protein position.
snpEff_genes.txt – a tab-delimited gene-level summary listing the number and types of variants affecting each gene.
snpEff_summary.html – an HTML report with variant type distributions, impact counts, and quality summaries.