AlphaGenome Atlas: in silico mutagenesis of the entire human genome improves prioritization and interpretation of non-coding variants

AlphaGenome Atlas is a comprehensive resource that enables joint interpretation and prioritization of variant effects across the entire human genome. Using this technology, researchers predicted regulatory effects on thousands of molecular phenotypes for every possible human single nucleotide variant and many observed indels. From these predictions, a unified AlphaGenome Variant Impact (AVI) score was derived and cis-regulatory motifs were mapped across the genome. AVI achieved state-of-the-art performance across diverse benchmarks with improved prioritization of deleterious non-coding variants. Application of this resource helped solve a rare epileptic encephalopathy case, increased statistical power to detect rare non-coding variants, and improved understanding of their mechanisms. AlphaGenome Atlas thus improves the prioritization and molecular interpretation of non-coding variants with genetic and clinical significance.