Submissions for variant NM_175914.5(HNF4A):c.50-5C>T

gnomAD frequency: 0.17964  dbSNP: rs745975

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000117237	SCV000316595	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000361090	SCV000433882	likely benign	Maturity onset diabetes mellitus in young	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000268875	SCV000433883	likely benign	Hyperinsulinism, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000710147	SCV000613648	benign	not provided	2017-07-12	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000117237	SCV001365799	benign	not specified	2019-04-24	criteria provided, single submitter	clinical testing	The c.95-5C>T variant in HNF4A is classified as benign because it has been identified in 19.56% (55114/281792) of total chromosomes by gnomAD (http://gnomad.broadinstitute.org/). Additionally, this variant does not alter the splice consensus sequence and is not predicted to impact splicing. ACMG/AMP criteria applied: BA1, BP4.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000710147	SCV001725049	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000710147	SCV001864384	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 10983627, 25266181)
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002226672	SCV002505503	benign	Glycosuria		criteria provided, single submitter	research	Mutations in HNF4A are associated with poor insulin secretion in response to hyperglycemia. These are associated with MODY1. Patients initially respond well to sulfonylureas but eventually become insulin dependent. As rs745975 SNP of HNF4α gene is associated with whole body insulin sensitivity and glucose tolerance and these factors are modulated by physical activity.
Ambry Genetics	RCV000361090	SCV002643574	benign	Maturity onset diabetes mellitus in young	2015-05-08	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Breakthrough Genomics, Breakthrough Genomics	RCV000710147	SCV005208725	likely benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000117237	SCV000151410	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.