Submissions for variant NM_000458.4(HNF1B):c.1339+17G>A

gnomAD frequency: 0.00006  dbSNP: rs374854968

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000517980	SCV000613643	uncertain significance	not specified	2017-01-26	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002464239	SCV002605564	likely benign	Maturity onset diabetes mellitus in young		criteria provided, single submitter	research	HNF1B gene mutations are associated with early onset diabetes and pancreatic atrophy. It is also associated with multiple renal manifestations including renal cysts, Tubulointerstitial disease, glomerulocystic disease, renal hypoplasia, hypomagnesemia. However no sufficient evidence is found to ascertain the role of this particular variant rs374854968, yet.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002527480	SCV003275324	likely benign	not provided	2024-08-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000517980	SCV003845009	likely benign	not specified	2023-02-20	criteria provided, single submitter	clinical testing	Variant summary: HNF1B c.1339+17G>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. 4/4 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 5.2e-05 in 251478 control chromosomes. The observed variant frequency is approximately 20.68 fold of the estimated maximal expected allele frequency for a pathogenic variant in HNF1B causing Maturity Onset Diabetes Of The Young 5 (Renal Cysts And Diabetes Syndrome) phenotype (2.5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1339+17G>A in individuals affected with Maturity Onset Diabetes Of The Young 5 (Renal Cysts And Diabetes Syndrome) and no experimental evidence demonstrating its impact on protein function have 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 one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.