ClinVar

Description

The NBN c.37+11A>G variant was not identified in the literature nor was it identified in the ClinVar, Cosmic, LOVD 3.0, and Zhejiang Colon Cancer Database. The variant was identified in dbSNP (ID: rs115032431) as “NA”, and in control databases in 425 (3 homozygous) of 272302 chromosomes at a frequency of 0.002 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 391 (3 homozygous) of 23526 chromosomes (freq: 0.02), Other in 3 of 6382 chromosomes (freq: 0.0005), Latino in 27 of 34324 chromosomes (freq: 0.0008), European Non-Finnish in 4 of 123086 chromosomes (freq: 0.00003), while not observed in the Ashkenazi Jewish, East Asian, European Finnish, and South Asian populations. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.