Improved SNP Annotation Parser for SnpEff-Annotated VCF Files

Overview

This Python script extracts and summarizes variant annotations from a SnpEff-annotated VCF file. It was developed as an extension of the variant annotation practical to provide a more flexible and informative method for investigating variants within a genomic region of interest.

Unlike the original practical script, which only reports missense variants and prints results directly to the terminal, this implementation:

• Produces a structured tab-delimited output file.
• Extracts additional annotation information including impact level, gene name, transcript information and HGVS nomenclature.
• Allows filtering by variant effect (e.g. missense variants only).
• Allows filtering by impact category (HIGH, MODERATE, LOW).
• Supports selection of known dbSNP variants only.
• Generates output suitable for downstream analysis in Excel, R or Python.

Requirements

Python 3.7 or later.

No external Python packages are required.

Input Files

The script expects a VCF file that has already been annotated using SnpEff.

Example:

ldlr_filtered_snps_final_ann_dbsnp.vcf

Usage

Basic usage:

python3 improved_parse_vcf_annotations.py \
ldlr_filtered_snps_final_ann_dbsnp.vcf \
11089462 \
11133820

Arguments:

Argument	Description
vcf_file	Annotated VCF file
gene_start	Start coordinate of target gene
gene_end	End coordinate of target gene

Output

By default the script creates:

improved_snp_annotations.tsv

The output table contains:

• Chromosome
• Position
• Variant ID
• Reference allele
• Alternate allele
• Quality score
• Filter status
• Read depth
• Allele frequency
• Variant effect
• Impact level
• Gene name
• Transcript ID
• Transcript biotype
• HGVS cDNA annotation
• HGVS protein annotation
• Protein position

Examples

Extract all variants within LDLR

python3 improved_parse_vcf_annotations.py \
ldlr_filtered_snps_final_ann_dbsnp.vcf \
11089462 \
11133820

Extract missense variants only

python3 improved_parse_vcf_annotations.py \
ldlr_filtered_snps_final_ann_dbsnp.vcf \
11089462 \
11133820 \
--effect missense_variant \
-o LDLR_missense.tsv

Extract HIGH impact variants only

python3 improved_parse_vcf_annotations.py \
ldlr_filtered_snps_final_ann_dbsnp.vcf \
11089462 \
11133820 \
--impact HIGH \
-o LDLR_high_impact.tsv

Extract known dbSNP variants only

python3 improved_parse_vcf_annotations.py \
ldlr_filtered_snps_final_ann_dbsnp.vcf \
11089462 \
11133820 \
--only-rs \
-o LDLR_known_rs.tsv

Comparison with Original Practical Script

Feature	Original Script	Improved Script
Region filtering	✓	✓
Missense variant detection	✓	✓
Transcript extraction	✓	✓
HGVS extraction	✓	✓
Terminal output	✓	✓
Structured output file	✗	✓
Impact filtering	✗	✓
dbSNP filtering	✗	✓
Additional annotations	✗	✓
Downstream analysis ready	✗	✓

Potential Future Improvements

Possible extensions include:

• Export to CSV and Excel formats.
• Functional consequence prioritisation.
• ClinVar annotation support.
• Protein domain annotation.
• PolyPhen and SIFT score integration.
• Automatic generation of summary statistics and plots.

Author

Edward Ying | Imperial College London, Biology

Developed as an extension of a variant annotation practical to improve exploration and interpretation of SnpEff-annotated VCF files.