rs6073425

Positions:

• chr20-44385286-C-T

Variant summary

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

The ENST00000316673.9(HNF4A):​c.50-20772C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 150,792 control chromosomes in the GnomAD database, including 4,978 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 0.23 (4978 hom., cov: 25)
• Consequence: HNF4A ENST00000316673.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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:49505): (HNF4A antisense RNA 1)

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 = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.50-20772C>T		intron_variant		ENST00000316673.9	NP_787110.2
HNF4A-AS1	NR_172878.1	n.211-614G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-20772C>T		intron_variant		1	NM_175914.5	ENSP00000315180
HNF4A-AS1	ENST00000452481.1	n.357-614G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34630 AN: 150692 Hom.: 4981 Cov.: 25

Gnomad AFR AF: 0.0780

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.00957

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.230 AC: 34614 AN: 150792 Hom.: 4978 Cov.: 25 AF XY: 0.226 AC XY: 16644 AN XY: 73596

Gnomad4 AFR AF: 0.0780

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.00939

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.255

Alfa AF: 0.296 Hom.: 1750

Bravo AF: 0.219

Asia WGS AF: 0.0750 AC: 262 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	5.1
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6073425; hg19: chr20-43013926;