Abstract Single nucleotide polymorphisms (SNPs) and small insertions/deletions (2-50bp) in genomic regulatory regions may impact function, and although widespread, they are largely unexplored in livestock. Here leveraging >500 epigenomic datasets from pigs, cattle, sheep, and chickens, 8-39 million variants were identified with candidate functional confidence. Using our Functional Confidence scoring system, these candidate functional variants were further ranked as High, Moderate, Low, Minimal, or Possible functional confidence by scoring for likelihood of disrupting transcription factor (TF)-chromatin binding based on their presence in eight genomic regulatory features. Predictive reliability analysis of estimated breeding values (EBVs) based on High/Moderate Confidence variants from pig shows a 23∼46% increase in reliability compared to EBVs based on general SNPs, illustrating the versatility of Functional Confidence scoring system for identifying potential functional variants in livestock. Therefore, we developed the Integrated Functional Mutation (IFmut) platform and embed the Functional Confidence scoring system for users to effortlessly navigate through epigenomic data or pinpoint specific genomic features/regions, uncover potential function of new variants or previously identified ones. Our work offers the scientific community a powerful and flexible tool, tailor-made for delving deep into variant function, setting a new benchmark in livestock research and breeding strategies.
