PT - JOURNAL ARTICLE AU - Thomas J. Nicholas AU - Michael J. Cormier AU - Aaron R. Quinlan TI - Annotation of structural variants with reported allele frequencies and related metrics from multiple datasets using SVAFotate AID - 10.1101/2022.06.09.495527 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.06.09.495527 4099 - http://biorxiv.org/content/early/2022/06/11/2022.06.09.495527.short 4100 - http://biorxiv.org/content/early/2022/06/11/2022.06.09.495527.full AB - Background Identification of impactful genetic variants from DNA sequencing data relies on increasingly detailed filtering strategies to isolate the small subset of variants that are more likely to underlie a disease phenotype. Datasets reflecting population allele frequencies of different types of variants have been demonstrated as powerful filtering tools, especially in the context of rare disease analysis. While such population-scale allele frequency datasets now exist for structural variants (SVs), it remains a challenge to match SV calls between multiple datasets and thereby correctly estimate the population allele frequency of a putative SV.Results We introduce SVAFotate, a software tool for SV matching that enables the annotation of SVs with variant allele frequency and related information. These annotations are derived from known SV datasets which are incorporated by SVAFotate. As a result, VCF files annotated by SVAFotate offer a variety of annotations to aid in the stratification of SVs as common or rare in the broader human population.Conclusions Here we demonstrate the use of SVAFotate in the classification of SVs with regards to their population frequency and illustrate how annotations provided by SVAFotate can be used to filter and prioritize SVs. Lastly, we detail how best to utilize these SV annotations in the analysis of genetic variation in studies of rare disease.Competing Interest StatementThe authors have declared no competing interest.AFAllele FrequencySVStructural VariantSNVSingle Nucleotide VariantINDELInsertion-DeletionWGSWhole-Genome SequencingDELDeletionDUPDuplicationINVInversionINSInsertionBNDUnclassified BreakendOFPOverlap Fraction Product