rs6031552

Positions:

• chr20-44361154-C-A

Variant summary

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

The NM_175914.5(HNF4A):​c.49+5301C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,010 control chromosomes in the GnomAD database, including 2,384 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 0.16 (2384 hom., cov: 31)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.49+5301C>A		intron_variant		ENST00000316673.9	NP_787110.2
HNF4A-AS1	NR_172878.1	n.361-233G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.49+5301C>A		intron_variant		1	NM_175914.5	ENSP00000315180
HNF4A	ENST00000457232.5	c.49+5301C>A		intron_variant		1		ENSP00000396216
HNF4A	ENST00000609262.5	c.-183+5301C>A		intron_variant		1		ENSP00000476310
HNF4A	ENST00000609795.5	c.49+5301C>A		intron_variant		1		ENSP00000476609

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24549 AN: 151892 Hom.: 2385 Cov.: 31

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.161 AC: 24546 AN: 152010 Hom.: 2384 Cov.: 31 AF XY: 0.160 AC XY: 11885 AN XY: 74304

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.161

Alfa AF: 0.182 Hom.: 320

Bravo AF: 0.155

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.4
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6031552; hg19: chr20-42989794;