20-44382185-A-G

Position:

• chr20-44382185-A-G

Variant summary

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

The NM_175914.5(HNF4A):​c.50-23873A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,696 control chromosomes in the GnomAD database, including 26,390 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 0.57 (26390 hom., cov: 31)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) 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	c.50-23873A>G		intron_variant		ENST00000316673.9	NP_787110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-23873A>G		intron_variant		1	NM_175914.5	ENSP00000315180.4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87118 AN: 151578 Hom.: 26357 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.575 AC: 87193 AN: 151696 Hom.: 26390 Cov.: 31 AF XY: 0.572 AC XY: 42392 AN XY: 74086

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.555

Alfa AF: 0.515 Hom.: 26519

Bravo AF: 0.565

Asia WGS AF: 0.518 AC: 1804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.70
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6017335; hg19: chr20-43010825;