ClinVar Miner

Submissions for variant NM_000207.3(INS):c.-153C>G

gnomAD frequency: 0.00019  dbSNP: rs915076855
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001769689 SCV002004585 uncertain significance not provided 2024-07-24 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on promoter activity (PMID: 20133622); Nucleotide is not conserved across species and the substitution has no predicted effect on splicing; Also known as c.-332C>G; This variant is associated with the following publications: (PMID: 20133622, 30977832)
Genetic Services Laboratory, University of Chicago RCV001821999 SCV002067365 uncertain significance not specified 2019-08-27 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV002290758 SCV002580772 likely pathogenic Maturity-onset diabetes of the young type 10 2022-04-28 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002506806 SCV002816827 uncertain significance Type 1 diabetes mellitus 2; Maturity-onset diabetes of the young type 10; Hyperproinsulinemia; Diabetes mellitus, permanent neonatal 4 2022-04-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001769689 SCV003439677 benign not provided 2023-03-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001821999 SCV004813500 likely benign not specified 2024-02-06 criteria provided, single submitter clinical testing Variant summary: INS c.-153C>G is located in the untranscribed region upstream of the INS gene region. Consensus agreement among computation 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 0.0002 in 308020 control chromosomes, predominantly at a frequency of 0.0028 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in INS causing Neonatal Diabetes Mellitus phenotype (recessive 0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.-153C>G has been reported in the literature in individuals affected with Neonatal Diabetes Mellitus or monogenic diabetes. These report(s) do not provide unequivocal conclusions about association of the variant with Neonatal Diabetes Mellitus. At least one publication reports experimental evidence evaluating an impact on promoter activity. The most pronounced variant effect results in about 35% of normal activity. The following publications have been ascertained in the context of this evaluation (PMID: 20133622, 30977832). ClinVar contains an entry for this variant (Variation ID: 1317682). Based on the evidence outlined above, the variant was classified as likely 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.