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NM_175914.5(HNF4A):c.353G>A (p.Arg118Gln) AND not specified

Germline classification:
Likely benign (1 submission)
Last evaluated:
Apr 21, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001420747.1

Allele description [Variation Report for NM_175914.5(HNF4A):c.353G>A (p.Arg118Gln)]

NM_175914.5(HNF4A):c.353G>A (p.Arg118Gln)

Gene:
HNF4A:hepatocyte nuclear factor 4 alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.12
Genomic location:
Preferred name:
NM_175914.5(HNF4A):c.353G>A (p.Arg118Gln)
HGVS:
  • NC_000020.11:g.44413727G>A
  • NG_009818.1:g.62927G>A
  • NM_000457.6:c.419G>A
  • NM_001030003.3:c.353G>A
  • NM_001030004.3:c.353G>A
  • NM_001258355.2:c.398G>A
  • NM_001287182.2:c.344G>A
  • NM_001287183.2:c.344G>A
  • NM_001287184.2:c.344G>A
  • NM_175914.5:c.353G>AMANE SELECT
  • NM_178849.3:c.419G>A
  • NM_178850.3:c.419G>A
  • NP_000448.3:p.Arg140Gln
  • NP_001025174.1:p.Arg118Gln
  • NP_001025175.1:p.Arg118Gln
  • NP_001245284.1:p.Arg133Gln
  • NP_001274111.1:p.Arg115Gln
  • NP_001274112.1:p.Arg115Gln
  • NP_001274113.1:p.Arg115Gln
  • NP_787110.2:p.Arg118Gln
  • NP_787110.2:p.Arg118Gln
  • NP_849180.1:p.Arg140Gln
  • NP_849181.1:p.Arg140Gln
  • LRG_483t1:c.353G>A
  • LRG_483:g.62927G>A
  • LRG_483p1:p.Arg118Gln
  • NC_000020.10:g.43042367G>A
  • NM_175914.4:c.353G>A
Protein change:
R115Q
Links:
dbSNP: rs764196059
NCBI 1000 Genomes Browser:
rs764196059
Molecular consequence:
  • NM_000457.6:c.419G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001030003.3:c.353G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001030004.3:c.353G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258355.2:c.398G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287182.2:c.344G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287183.2:c.344G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287184.2:c.344G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_175914.5:c.353G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178849.3:c.419G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_178850.3:c.419G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001623090Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely benign
(Apr 21, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular genetic testing of patients with monogenic diabetes and hyperinsulinism.

Bennett JT, Vasta V, Zhang M, Narayanan J, Gerrits P, Hahn SH.

Mol Genet Metab. 2015 Mar;114(3):451-8. doi: 10.1016/j.ymgme.2014.12.304. Epub 2014 Dec 20.

PubMed [citation]
PMID:
25555642
PMCID:
PMC7852340

Six years' experience with LipidSeq: clinical and research learnings from a hybrid, targeted sequencing panel for dyslipidemias.

Dron JS, Wang J, McIntyre AD, Iacocca MA, Robinson JF, Ban MR, Cao H, Hegele RA.

BMC Med Genomics. 2020 Feb 10;13(1):23. doi: 10.1186/s12920-020-0669-2.

PubMed [citation]
PMID:
32041611
PMCID:
PMC7011550

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001623090.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: HNF4A c.353G>A (p.Arg118Gln) 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 5.7e-05 in 282370 control chromosomes (gnomAD). The observed variant frequency is approximately 18 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 benign. c.353G>A has been reported in the literature in individuals undergoing testing for testing for pancreatic beta cell disorders or testing to identify the genetic determinants of dyslipidemia and metabolic disorders (Bennett_2015, Dron_2020). These reports however, do not provide unequivocal conclusions about association of the variant with Maturity Onset Diabetes Of The Young 1/Neonatal Diabetes Mellitus. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024