ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.75G>A (p.Ala25=) (rs543230518)

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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000282784 SCV000332642 benign not specified 2015-07-15 criteria provided, single submitter clinical testing
GeneDx RCV000282784 SCV000522965 likely benign not specified 2016-01-04 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.
Invitae RCV000556534 SCV000627992 benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000776294 SCV000911588 benign Familial thoracic aortic aneurysm and aortic dissection 2018-10-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000282784 SCV001363507 benign not specified 2019-06-10 criteria provided, single submitter clinical testing Variant summary: FBN1 c.75G>A alters a conserved nucleotide resulting in a synonymous change. 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 0.00056 in 251464 control chromosomes, predominantly at a frequency of 0.0046 within the South Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 41-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in FBN1 causing Aortopathy phenotype (0.00011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.75G>A in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.

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.