ClinVar

Description

The NBN c.37+10G>C variant was not identified in the literature nor was it identified in Cosmic, LOVD 3.0, Zhejiang Colon Cancer Database. The variant was identified in dbSNP (ID: rs369408590) as “With other allele”, ClinVar (as uncertain significance by Illumina, likely benign by Invitae, and benign by GeneDx), and Clinvitae (3x) databases. The variant was identified in control databases in 26 of 272116 chromosomes at a frequency of 0.000096 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 1 of 23486 chromosomes (freq: 0.000043), European (Non-Finnish) in 9 of 122980 chromosomes (freq: 0.000073), and Ashkenazi Jewish in 16 of 10068 chromosomes (freq: 0.001589), while the variant was not observed in the Other, Latino, East Asian, European Finnish, and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.