ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.1760-4G>A (rs79662406)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000246189 SCV000513593 likely benign not specified 2017-10-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000246189 SCV000917631 likely benign not specified 2018-10-05 criteria provided, single submitter clinical testing Variant summary: MEFV c.1760-4G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0016 in 276732 control chromosomes, predominantly within the African subpopulation at a frequency of 0.017 in the gnomAD database, including 7 homozygotes. This frequency is not higher than expected for a pathogenic variant in MEFV causing Familial Mediterranean Fever (0.0016 vs 0.022), although close and with numerous homozygotes, suggesting the variant may be benign. The variant, c.1760-4G>A, has been reported in the literature in and characterized as likely benign (Van Gijn_2018). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000083710 SCV000629028 benign Familial Mediterranean fever 2017-11-22 criteria provided, single submitter clinical testing
PreventionGenetics RCV000246189 SCV000303121 benign not specified criteria provided, single submitter clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083710 SCV000115802 not provided Familial Mediterranean fever no assertion provided not provided

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.