rs6073425

Variant names:

• chr20-44385286-C-T
• rs6073425
• NM_175914.5:c.50-20772C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175914.5(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 NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.50-20772C>T		intron_variant	Intron 1 of 9	ENST00000316673.9	NP_787110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-20772C>T		intron_variant	Intron 1 of 9	1	NM_175914.5	ENSP00000315180.4

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

African (AFR) AF: 0.0780 AC: 3210 AN: 41128

American (AMR) AF: 0.224 AC: 3386 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3468

East Asian (EAS) AF: 0.00939 AC: 48 AN: 5110

South Asian (SAS) AF: 0.104 AC: 492 AN: 4724

European-Finnish (FIN) AF: 0.292 AC: 3012 AN: 10300

Middle Eastern (MID) AF: 0.288 AC: 83 AN: 288

European-Non Finnish (NFE) AF: 0.331 AC: 22423 AN: 67670

Other (OTH) AF: 0.255 AC: 531 AN: 2082

Alfa AF: 0.239 Hom.: 3494

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
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6073425; hg19: chr20-43013926;