20-44412275-A-C

Position:

• chr20-44412275-A-C

Variant summary

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

The NM_175914.5(HNF4A):​c.320-1419A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,908 control chromosomes in the GnomAD database, including 8,119 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 0.32 (8119 hom., cov: 31)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.320-1419A>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.320-1419A>C		intron_variant		1	NM_175914.5	ENSP00000315180

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49243 AN: 151790 Hom.: 8102 Cov.: 31

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.324 AC: 49277 AN: 151908 Hom.: 8119 Cov.: 31 AF XY: 0.327 AC XY: 24260 AN XY: 74244

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.332

Alfa AF: 0.316 Hom.: 2617

Bravo AF: 0.309

Asia WGS AF: 0.367 AC: 1275 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	3.1
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6073432; hg19: chr20-43040915;