Benign-Ex: Delineating Regions of the Human Genome Benign to Copy Number Variation

Abstract

AbstractWhile copy number variants (CNVs) have been identified as an important cause of rare genetic disorders, they have also been identified in unaffected control populations, making clinical interpretation of these lesions challenging. Discriminating benign CNVs from those pathogenic for rare genetic disorders, therefore, relies on understanding what regions of the human genome are tolerant to copy number variation. Benign-Ex is a python-based program that uses information from databases of CNVs to generate one or more benign interval map(s) and then identifies the optimal map by computing the overlap with known pathogenic regions. We utilized Benign-Ex to identify the optimal set of benign intervals from two distinct CNV databases: Database of Genomic Variants (DGV) and Clinical Genome Resource (ClinGen). Benign-Ex called 41.1% of the genome benign using data from DGV and 37.6% of the genome benign using data from ClinGen. The benign regions from DGV and ClinGen werenotspatially correlated, underscoring the importance of integrating both research and clinical databases for determining CNV benignity.