rs4812831

Positions:

• chr20-44389620-G-A

Variant summary

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

The NM_175914.5(HNF4A):​c.50-16438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,180 control chromosomes in the GnomAD database, including 1,970 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 0.13 (1970 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

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)

(HGNC:):

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 = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF4A	NM_175914.5	c.50-16438G>A		intron_variant		ENST00000316673.9
HNF4A-AS1	NR_172878.1	n.211-4948C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-16438G>A		intron_variant		1	NM_175914.5
HNF4A-AS1	ENST00000452481.1	n.356+2389C>T		intron_variant, non_coding_transcript_variant		1
	ENST00000455642.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19459 AN: 152042 Hom.: 1959 Cov.: 32

Gnomad AFR AF: 0.0581

Gnomad AMI AF: 0.0936

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.100 AC: 2 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.128 AC: 19491 AN: 152160 Hom.: 1970 Cov.: 32 AF XY: 0.137 AC XY: 10160 AN XY: 74368

Gnomad4 AFR AF: 0.0580

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.126

Alfa AF: 0.126 Hom.: 3193

Bravo AF: 0.139

Asia WGS AF: 0.302 AC: 1050 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	3.4
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4812831; hg19: chr20-43018260;