rs6130609

Positions:

• chr20-44404455-G-C

Variant summary

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

The NM_175914.5(HNF4A):​c.50-1603G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,920 control chromosomes in the GnomAD database, including 5,205 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 0.24 (5205 hom., cov: 32)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.50-1603G>C		intron_variant		ENST00000316673.9	NP_787110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-1603G>C		intron_variant		1	NM_175914.5	ENSP00000315180

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36898 AN: 151804 Hom.: 5189 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.243 AC: 36941 AN: 151920 Hom.: 5205 Cov.: 32 AF XY: 0.253 AC XY: 18755 AN XY: 74234

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.233

Alfa AF: 0.211 Hom.: 474

Bravo AF: 0.244

Asia WGS AF: 0.480 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs6130609; hg19: chr20-43033095;