ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.451-5T>G (rs774098604)

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 RCV000634822 SCV000756166 likely benign Alstrom syndrome 2020-11-16 criteria provided, single submitter clinical testing
Counsyl RCV000634822 SCV000797915 uncertain significance Alstrom syndrome 2018-02-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193872 SCV001363030 likely benign not specified 2019-11-04 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.451-5T>G (also known as c.454-5T>G) 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. 3/5 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 0.00014 in 248930 control chromosomes, predominantly at a frequency of 0.0019 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in ALMS1 causing Alstrom Syndrome phenotype (0.0014), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.451-5T>G has been reported in the literature in individuals affected with Alstrom Syndrome, retinitis pigmentosa and in an individual affected with combined 17 alpha hydroxylase/17,20-lyase deficiency without strong evidence of causality (Marshall_2015, Xu_2016, Zhang_2018) . These reports however, do not provide unequivocal conclusions about association of the variant with Alstrom Syndrome. 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. One laboratory classified the variant as likely benign, and the other as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Natera, Inc. RCV000634822 SCV001453433 likely benign Alstrom syndrome 2020-01-09 no assertion criteria provided 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.