ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.37+6G>C (rs540868733)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231974 SCV000287470 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2018-10-22 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the NBN gene. It does not directly change the encoded amino acid sequence of the NBN protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs540868733, ExAC 0.009%). This variant has not been reported in the literature in individuals with NBN-related disease. ClinVar contains an entry for this variant (Variation ID: 239196). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000581181 SCV000690713 likely benign Hereditary cancer-predisposing syndrome 2017-02-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590289 SCV000697967 uncertain significance not provided 2017-08-16 criteria provided, single submitter clinical testing Variant summary: The NBN c.37+6G>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. Additionally, ESE finder predicts the creation of SF2/ASF and SRp55 binding sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 2/112342 control chromosomes at a frequency of 0.0000178, which does not exceed the estimated maximal expected allele frequency of a pathogenic NBN variant (0.0025). In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS).
Counsyl RCV000231974 SCV000791592 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2017-05-15 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.