chr20-44355761-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_175914.5(HNF4A):c.-44C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,601,216 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 4 hom. )
Consequence
HNF4A
NM_175914.5 5_prime_UTR
NM_175914.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.355
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000788 (12/152366) while in subpopulation SAS AF= 0.00165 (8/4834). AF 95% confidence interval is 0.000823. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNF4A | NM_175914.5 | c.-44C>T | 5_prime_UTR_variant | 1/10 | ENST00000316673.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNF4A | ENST00000316673.9 | c.-44C>T | 5_prime_UTR_variant | 1/10 | 1 | NM_175914.5 | |||
HNF4A | ENST00000457232.5 | upstream_gene_variant | 1 | ||||||
HNF4A | ENST00000609262.5 | upstream_gene_variant | 1 | ||||||
HNF4A | ENST00000609795.5 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152248Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000197 AC: 48AN: 243560Hom.: 1 AF XY: 0.000301 AC XY: 40AN XY: 132980
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GnomAD4 exome AF: 0.000126 AC: 182AN: 1448850Hom.: 4 Cov.: 29 AF XY: 0.000177 AC XY: 128AN XY: 721378
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 02, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at