Variant 20-44406020-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000316673.9(HNF4A):c.50-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,592,492 control chromosomes in the GnomAD database, including 170,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16380 hom., cov: 33)

Exomes 𝑓: 0.45 ( 153636 hom. )

Consequence

HNF4A
ENST00000316673.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.608

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=-0.85).

BP6

Variant 20-44406020-T-C is Benign according to our data. Variant chr20-44406020-T-C is described in ClinVar as [Benign]. Clinvar id is 673538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-44406020-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF4A	NM_175914.5 linkuse as main transcript	c.50-38T>C		intron_variant		ENST00000316673.9	NP_787110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9 linkuse as main transcript	c.50-38T>C		intron_variant		1	NM_175914.5	ENSP00000315180		P41235-5

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69419

AN:

151974

Hom.:

16354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.501

AC:

124241

AN:

248142

Hom.:

33100

AF XY:

0.505

AC XY:

67915

AN XY:

134460

show subpopulations

Gnomad AFR exome

AF:

0.450

Gnomad AMR exome

AF:

0.538

Gnomad ASJ exome

AF:

0.424

Gnomad EAS exome

AF:

0.793

Gnomad SAS exome

AF:

0.668

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.423

Gnomad OTH exome

AF:

0.456

GnomAD4 exome

AF:

0.453

AC:

652667

AN:

1440400

Hom.:

153636

Cov.:

AF XY:

0.459

AC XY:

329699

AN XY:

717758

show subpopulations

Gnomad4 AFR exome

AF:

0.442

Gnomad4 AMR exome

AF:

0.526

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.766

Gnomad4 SAS exome

AF:

0.662

Gnomad4 FIN exome

AF:

0.450

Gnomad4 NFE exome

AF:

0.423

Gnomad4 OTH exome

AF:

0.464

GnomAD4 genome

AF:

0.457

AC:

69488

AN:

152092

Hom.:

16380

Cov.:

AF XY:

0.462

AC XY:

34389

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.448

Gnomad4 AMR

AF:

0.473

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.777

Gnomad4 SAS

AF:

0.675

Gnomad4 FIN

AF:

0.444

Gnomad4 NFE

AF:

0.422

Gnomad4 OTH

AF:

0.451

Alfa

AF:

0.429

Hom.:

20322

Bravo

AF:

0.456

Asia WGS

AF:

0.686

AC:

2384

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -

Maturity onset diabetes mellitus in young

Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Potent mutations in HNF4A are associated with poor insulin secretion in response to hyperglycemia. Associated with MODY1. Patients initially respond well to sulfonylureas but eventually become insulin dependent. However, more evidence is required to ascertain the role of this particular variant rs736824 in MODY, yet. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.1

DANN

Benign

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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