rs772959288
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_175914.5(HNF4A):c.369G>A(p.Glu123=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
HNF4A
NM_175914.5 synonymous
NM_175914.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.305
Genes affected
HNF4A (HGNC:5024): (hepatocyte nuclear factor 4 alpha) The protein encoded by this gene is a nuclear transcription factor which binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene may play a role in development of the liver, kidney, and intestines. Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitus type I. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 20-44413743-G-A is Benign according to our data. Variant chr20-44413743-G-A is described in ClinVar as [Benign]. Clinvar id is 586014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.305 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF4A | NM_175914.5 | c.369G>A | p.Glu123= | synonymous_variant | 4/10 | ENST00000316673.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF4A | ENST00000316673.9 | c.369G>A | p.Glu123= | synonymous_variant | 4/10 | 1 | NM_175914.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152040Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000518 AC: 13AN: 250996Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135696
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461804Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727196
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152040Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74256
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 26, 2024 | - - |
Maturity onset diabetes mellitus in young Benign:1
Benign, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Potent mutations in HNF4A are associated with poor insulin secretion in response to hyperglycemia. Associated with MODY1. Patients initially respond well to sulfonylureas but eventually become insulin dependent. However, more evidence is required to ascertain the role of this particular variant rs772959288 in MODY, yet. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 05, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at