Genomic Sequence Variant Annotation Framework

Architect a PHP-based genomic variant annotation system that can process large-scale VCF (Variant Call Format) files, integrating multiple annotation databases like ClinVar, dbSNP, and COSMIC. Build a modular system using Laravel that can parse complex genomic data structures, perform variant effect predictions, and generate comprehensive reports. Implement a background processing queue that can handle multi-gigabyte genomic files, with support for parallel processing and incremental annotation updates. Include robust error handling for malformed genetic data and provide an extensible plugin architecture for adding new annotation sources.