ClinVar

Description

The NBN p.Thr273= variant was not identified in the literature nor was it identified in the LOVD 3.0, or Zhejiang Colon Cancer Database. The variant was identified in the following databases: dbSNP (ID: rs147660518) as With Likely benign allele, ClinVar (classified as likely benign by Invitae, Ambry Genetics), and Clinvitae (classified as likely benign by Invitae and ClinVar). The variant was identified in control databases in 18 of 277090 chromosomes at a frequency of 0.000065, in the following populations: European Non-Finnish in 15 of 126628 chromosomes (freq. 0.0001), Latino in 2 of 34386 chromosomes (freq. 0.0001), African in 1 of 24030 chromosomes (freq.0.00004) (Genome Aggregation Consortium Feb 27, 2017). The p.Thr273= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site, however 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing (loss); this information is not predictive enough to assume pathogenicity. 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.