rs11086926

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_175914.5(HNF4A):c.*392T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 206,482 control chromosomes in the GnomAD database, including 1,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1767 hom., cov: 32)

Exomes 𝑓: 0.058 ( 139 hom. )

Consequence

HNF4A
NM_175914.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0710

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]

HNF4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 20-44430057-T-G is Benign according to our data. Variant chr20-44430057-T-G is described in ClinVar as [Benign]. Clinvar id is 338440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF4A	NM_175914.5 linkuse as main transcript	c.*392T>G		3_prime_UTR_variant	10/10	ENST00000316673.9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF4A	ENST00000316673.9 linkuse as main transcript	c.*392T>G	3_prime_UTR_variant	10/10	1	NM_175914.5		P41235-5
HNF4A	ENST00000316099.10 linkuse as main transcript	c.*392T>G	3_prime_UTR_variant	10/10	1			P41235-1
HNF4A	ENST00000415691.2 linkuse as main transcript	c.*392T>G	3_prime_UTR_variant	10/10	1		P1	P41235-2
HNF4A	ENST00000372920.1 linkuse as main transcript	c.*1584T>G	3_prime_UTR_variant, NMD_transcript_variant	11/11	1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19185

AN:

152050

Hom.:

1760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.0345

Gnomad SAS

AF:

0.0992

Gnomad FIN

AF:

0.0610

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0691

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.0583

AC:

3167

AN:

54314

Hom.:

139

Cov.:

AF XY:

0.0592

AC XY:

1653

AN XY:

27938

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.0379

Gnomad4 EAS exome

AF:

0.0309

Gnomad4 SAS exome

AF:

0.0598

Gnomad4 FIN exome

AF:

0.0413

Gnomad4 NFE exome

AF:

0.0511

Gnomad4 OTH exome

AF:

0.0688

GnomAD4 genome

AF:

0.126

AC:

19211

AN:

152168

Hom.:

1767

Cov.:

AF XY:

0.124

AC XY:

9220

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.131

Gnomad4 ASJ

AF:

0.0499

Gnomad4 EAS

AF:

0.0349

Gnomad4 SAS

AF:

0.0982

Gnomad4 FIN

AF:

0.0610

Gnomad4 NFE

AF:

0.0691

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0965

Hom.:

457

Bravo

AF:

0.138

Asia WGS

AF:

0.0890

AC:

309

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial hyperinsulinism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Maturity-onset diabetes of the young type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

2.3

Dann

Benign

0.50

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over