Analysis of Germline Variants with Low Allele Frequencies in Turkish Healthy Cohort

BACKGROUND/AIMS: Within a specific population, rare variants with minor allele frequencies (MAFs) below 0.01% may underlie a particular genetic disorder when Mendelian diseases are investigated.Although MAFs can be determined by universal databases, the importance of a variant with a low MAF may vary across populations.Hence, documentation of rare variants in healthy individuals could be remarkably valuable.However, such approaches have not yet been applied in the Turkish population.Thus, we aimed to identify rare germline variants in a healthy Turkish population. MATERIALS AND METHODS:We re-analyzed whole-exome sequencing data from 80 healthy Turkish individuals and filtered variants using a MAF threshold of <0.01%.We further assessed the pathogenicity of the filtered variants according to the American College of Medical Genetics criteria.RESULTS: There were numerous rare variants, some of which were common to all participants.Importantly, those variants were classified as of unknown significance or as likely pathogenic; however, this classification should be revised because the variants were observed in healthy individuals. CONCLUSION:We propose that these variants could be benign, as they were detected in healthy Turkish participants.Finally, the rare variants in the Turkish population should still be reported to guide clinicians during routine molecular diagnosis.