rs6031593

Positions:

• chr20-44422573-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175914.5(HNF4A):​c.827-1445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,406 control chromosomes in the GnomAD database, including 23,081 homozygotes. 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: 𝑓 0.55 (23081 hom., cov: 30)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF4A	NM_175914.5	c.827-1445T>C		intron_variant		ENST00000316673.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF4A	ENST00000316673.9	c.827-1445T>C		intron_variant		1	NM_175914.5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 82988 AN: 151298 Hom.: 23075 Cov.: 30

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.548 AC: 83028 AN: 151406 Hom.: 23081 Cov.: 30 AF XY: 0.542 AC XY: 40119 AN XY: 73960

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.575

Alfa AF: 0.582 Hom.: 43486

Bravo AF: 0.546

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6031593; hg19: chr20-43051213;