A study of normal copy number variations in Israeli population

Hum Genet. 2021 Mar;140(3):553-563. doi: 10.1007/s00439-020-02225-4. Epub 2020 Sep 27.


The population of Israel is ethnically diverse, and individuals from different ethnic groups share specific genetic variations. These variations, which have been passed on from common ancestors, are usually reported in public databases as rare variants. Here, we aimed to identify ethnicity-based benign copy number variants (CNVs) and generate the first Israeli CNV database. We applied a data-mining approach to the results of 10,193 chromosomal microarray tests, of which 2150 tests were from individuals of 13 common ethnic backgrounds (n ≥ 10). We found 165 CNV regions (> 50 kbp) that are unique to specific ethnic groups (uCNVRs). The frequency of more than 19% of these uCNVRs is between 1 and 20% of the common ethnic origin, while their frequency in the overall cohort is between 0.5 and 1.6%. Of these 165 uCNVRs, 98 are reported as variants of unknown significance or as not available in dbVar; we postulate that these uCNVRs should be annotated as either "likely benign" or "benign". The ethnic-specific CNVs extracted in this study will allow geneticists to distinguish between relevant pathogenic genomic aberrations and benign ethnicity-related variations, thus preventing variant misinterpretation that may lead to unnecessary pregnancy terminations.

Keywords: Chromosomal microarray analysis (CMA); Copy number variations (CNV); Data mining; Ethnicity; Polymorphism; dbVar.

MeSH terms

  • DNA Copy Number Variations*
  • Female
  • Humans
  • Israel
  • Jews / genetics*
  • Male