rs4364072

Positions:

• chr20-44385326-A-G
• chr20-44385326-A-T

Variant summary

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

The NM_175914.5(HNF4A):​c.50-20732A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,112 control chromosomes in the GnomAD database, including 8,639 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 0.33 (8639 hom., cov: 28)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.50-20732A>G		intron_variant		ENST00000316673.9	NP_787110.2
HNF4A-AS1	NR_172878.1	n.211-654T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-20732A>G		intron_variant		1	NM_175914.5	ENSP00000315180
HNF4A-AS1	ENST00000452481.1	n.357-654T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 49927 AN: 150992 Hom.: 8626 Cov.: 28

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.331 AC: 49962 AN: 151112 Hom.: 8639 Cov.: 28 AF XY: 0.331 AC XY: 24410 AN XY: 73800

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.315

Alfa AF: 0.295 Hom.: 6637

Bravo AF: 0.324

Asia WGS AF: 0.374 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.0
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4364072; hg19: chr20-43013966;