rs2071197

Positions:

• chr20-44401795-G-A
• chr20-44401795-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_175914.5(HNF4A):​c.50-4263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,216 control chromosomes in the GnomAD database, including 1,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1793 hom., cov: 32)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.43

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-44401795-G-A is Benign according to our data. Variant chr20-44401795-G-A is described in ClinVar as [Benign]. Clinvar id is 667605.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.50-4263G>A		intron_variant		ENST00000316673.9	NP_787110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-4263G>A		intron_variant		1	NM_175914.5	ENSP00000315180

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17272 AN: 152098 Hom.: 1780 Cov.: 32

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.114 AC: 17301 AN: 152216 Hom.: 1793 Cov.: 32 AF XY: 0.121 AC XY: 8976 AN XY: 74388

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.0496

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.116

Alfa AF: 0.108 Hom.: 1591

Bravo AF: 0.116

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0080
DANN	Benign	0.60

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: rs2071197; hg19: chr20-43030435;