rs879092890

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS2_Supporting

The NM_175914.5(HNF4A):​c.-83C>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000451 in 1,107,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

HNF4A
NM_175914.5 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.60
Variant links:
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 Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BS2
High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HNF4ANM_175914.5 linkc.-83C>G 5_prime_UTR_variant Exon 1 of 10 ENST00000316673.9 NP_787110.2 P41235-5F1D8T0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HNF4AENST00000316673 linkc.-83C>G 5_prime_UTR_variant Exon 1 of 10 1 NM_175914.5 ENSP00000315180.4 P41235-5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000451
AC:
5
AN:
1107566
Hom.:
0
Cov.:
15
AF XY:
0.00000353
AC XY:
2
AN XY:
566922
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000382
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
CADD
Benign
19
DANN
Benign
0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs879092890; hg19: chr20-42984362; API