ClinVar Genomic variation as it relates to human health
NM_175914.5(HNF4A):c.50-5C>T
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_175914.5(HNF4A):c.50-5C>T
Variation ID: 129239 Accession: VCV000129239.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20q13.12 20: 44406053 (GRCh38) [ NCBI UCSC ] 20: 43034693 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 6, 2014 May 1, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_175914.5:c.50-5C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_000457.6:c.116-5C>T intron variant NM_001030003.3:c.50-5C>T intron variant NM_001030004.3:c.50-5C>T intron variant NM_001258355.2:c.95-5C>T intron variant NM_001287182.2:c.41-5C>T intron variant NM_001287183.2:c.41-5C>T intron variant NM_001287184.2:c.41-5C>T intron variant NM_178849.3:c.116-5C>T intron variant NM_178850.3:c.116-5C>T intron variant NC_000020.11:g.44406053C>T NC_000020.10:g.43034693C>T NG_009818.1:g.55253C>T LRG_483:g.55253C>T LRG_483t1:c.50-5C>T LRG_483t2:c.116-5C>T - Protein change
- Other names
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- Canonical SPDI
- NC_000020.11:44406052:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.16873 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.19746
Exome Aggregation Consortium (ExAC) 0.20079
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.19045
1000 Genomes Project 30x 0.16740
1000 Genomes Project 0.16873
Trans-Omics for Precision Medicine (TOPMed) 0.17668
The Genome Aggregation Database (gnomAD) 0.17964
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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HNF4A | - | - |
GRCh38 GRCh37 |
574 | 587 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign (3) |
criteria provided, multiple submitters, no conflicts
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Apr 24, 2019 | RCV000117237.18 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000268875.6 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jun 14, 2016 | RCV000361090.8 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000710147.12 | |
Benign (1) |
criteria provided, single submitter
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- | RCV002226672.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Jul 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV000613648.2
First in ClinVar: Oct 02, 2016 Last updated: Oct 19, 2018 |
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Benign
(Apr 24, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV001365799.1
First in ClinVar: Jul 04, 2020 Last updated: Jul 04, 2020 |
Comment:
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 … (more)
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. (less)
Number of individuals with the variant: 1
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Benign
(Mar 03, 2015)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001864384.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 10983627, 25266181)
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Benign
(-)
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criteria provided, single submitter
Method: research
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Glycosuria
Affected status: yes
Allele origin:
somatic
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Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV002505503.1
First in ClinVar: May 07, 2022 Last updated: May 07, 2022 |
Comment:
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 … (more)
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. (less)
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Benign
(May 08, 2015)
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criteria provided, single submitter
Method: clinical testing
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Maturity onset diabetes mellitus in young
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002643574.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
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 … (more)
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. (less)
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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000316595.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Likely benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Maturity Onset Diabetes of the Young
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000433882.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Likely benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hyperinsulinism, Dominant
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000433883.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001725049.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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AllHighlyPenetrant
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000151410.2
First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014 |
Comment:
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 … (more)
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. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Pyruvate Dehydrogenase Phosphatase Regulatory Gene Expression Correlates with Exercise Training Insulin Sensitivity Changes. | Barberio MD | Medicine and science in sports and exercise | 2016 | PMID: 27846149 |
Interaction between HNF4A polymorphisms and physical activity in relation to type 2 diabetes-related traits: results from the Quebec Family Study. | Ruchat SM | Diabetes research and clinical practice | 2009 | PMID: 19406499 |
Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus. | Plengvidhya N | Clinical endocrinology | 2009 | PMID: 18811724 |
Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain. | Estalella I | Clinical endocrinology | 2007 | PMID: 17573900 |
Novel genetic variations and haplotypes of hepatocyte nuclear factor 4alpha (HNF4A) found in Japanese type II diabetic patients. | Fukushima-Uesaka H | Drug metabolism and pharmacokinetics | 2006 | PMID: 16946562 |
[Scanning the HNF4A gene mutation from Chinese pedigrees with early- and/or multiple-onset diabetes]. | Zhang R | Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics | 2006 | PMID: 16883527 |
Genetic analysis of HNF4A polymorphisms in Caucasian-American type 2 diabetes. | Bagwell AM | Diabetes | 2005 | PMID: 15793260 |
Mutations in the hepatocyte nuclear factor-4alpha gene in Japanese with non-insulin-dependent diabetes: a nucleotide substitution in the polypyrimidine tract of intron 1b. | Sakurai K | Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme | 2000 | PMID: 10983627 |
A missense mutation in hepatocyte nuclear factor-4 alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus. | Hani EH | The Journal of clinical investigation | 1998 | PMID: 9449683 |
Organization and partial sequence of the hepatocyte nuclear factor-4 alpha/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY. | Furuta H | Diabetes | 1997 | PMID: 9313765 |
Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM. | Møller AM | Diabetologia | 1997 | PMID: 9267996 |
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Text-mined citations for rs745975 ...
HelpRecord last updated Jun 23, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.