csq

csq predicts haplotype-aware functional consequences of genetic variants to account for compound variants and frame-restoring indels in coding sequences.

Key Features:

• Haplotype-aware analysis: Leverages known haplotype/phase information to resolve compound variants and cases where adjacent variants or frame-shifting indels followed by frame-restoring indels alter codons or coding frames.
• Efficiency and performance: Demonstrates substantially improved computational performance, reported as an order of magnitude faster and requiring significantly less memory than existing tools.
• Integration with BCFtools: Implemented as BCFtools/csq and integrates consequence calling within the BCFtools package.

Scientific Applications:

• Variant categorization and prioritization: Provides more accurate consequence predictions to improve prioritization of potentially pathogenic variants in clinical and research analyses.
• Genomic research on complex haplotypes: Enables precise interpretation of compound variants and complex haplotypes, including analyses involving structural variation.

Methodology:

BCFtools/csq integrates known phase information into its consequence prediction algorithms and adjusts predictions based on the context of adjacent genetic variants within haplotypes; in testing with data from the 1000 Genomes Project it altered consequence predictions for 501 compound variants identified among 81.7 million variants across 139 average compound variants per haplotype.