ClinVar Miner

Submissions for variant NM_175914.5(HNF4A):c.1321A>G (p.Ile441Val)

gnomAD frequency: 0.00006  dbSNP: rs147638455
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030015 SCV000052670 uncertain Maturity-onset diabetes of the young type 1 2011-08-18 criteria provided, single submitter curation Converted during submission to Uncertain significance.
Eurofins NTD LLC (GA) RCV000725499 SCV000337348 uncertain significance not provided 2015-11-16 criteria provided, single submitter clinical testing
GeneDx RCV000725499 SCV000589599 likely benign not provided 2021-05-05 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 23227446, 27884173, 24097065, 25905084, 26059258, 10227563, 21105491, 10768098, 31264968, 31595705)
Fulgent Genetics,Fulgent Genetics RCV000764241 SCV000895244 uncertain significance Maturity-onset diabetes of the young type 1; Type 2 diabetes mellitus; Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young 2018-10-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000030015 SCV001302393 uncertain significance Maturity-onset diabetes of the young type 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services,Illumina RCV001142000 SCV001302394 uncertain significance Familial hyperinsulinism 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Athena Diagnostics Inc RCV000725499 SCV001475904 likely benign not provided 2019-12-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001358754 SCV001554611 likely benign not specified 2021-03-30 criteria provided, single submitter clinical testing Variant summary: HNF4A c.1321A>G (p.Ile441Val) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00037 in 251452 control chromosomes, predominantly at a frequency of 0.00072 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 230 fold of the estimated maximal expected allele frequency for a pathogenic variant in HNF4A causing Maturity Onset Diabetes of the Young 1/Neonatal Diabetes Mellitus phenotype (3.1e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. c.1321A>G has been reported in the literature (example: deSantana_2019, Majidi_2018). These reports however, do not provide unequivocal conclusions about association of the variant with Maturity Onset Diabetes of the Young 1/Neonatal Diabetes Mellitus. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Guo_2019). Five ClinVar submitters (evaluation after 2014) cite the variant as likely benign (n=1) or uncertain significance (n=4). Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen RCV000725499 SCV001747309 likely benign not provided 2021-04-01 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV001358754 SCV002067858 likely benign not specified 2021-11-04 criteria provided, single submitter clinical testing
Invitae RCV000725499 SCV002293203 uncertain significance not provided 2021-09-17 criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics RCV000725499 SCV002503561 uncertain significance not provided 2021-02-21 criteria provided, single submitter clinical testing
Laboratory of Gastroenterology and Hepatology,Radboud University Medical Center RCV001844803 SCV001877068 uncertain significance Autosomal dominant polycystic liver disease 2021-09-01 no assertion criteria provided research

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