20-44395409-G-T

Position:

• chr20-44395409-G-T

Variant summary

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

The NM_175914.5(HNF4A):​c.50-10649G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,334 control chromosomes in the GnomAD database, including 15,263 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 0.42 (15250 hom., cov: 33)
  • Exomes 𝑓: 0.50 (13 hom.)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF4A	NM_175914.5	c.50-10649G>T		intron_variant		ENST00000316673.9
HNF4A-AS1	NR_172878.1	n.210+44C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-10649G>T		intron_variant		1	NM_175914.5
HNF4A-AS1	ENST00000452481.1	n.254+44C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 64102 AN: 152112 Hom.: 15239 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.500 AC: 51 AN: 102 Hom.: 13 Cov.: 0 AF XY: 0.480 AC XY: 24 AN XY: 50

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.833

Gnomad4 EAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.421 AC: 64129 AN: 152232 Hom.: 15250 Cov.: 33 AF XY: 0.424 AC XY: 31528 AN XY: 74418

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.452

Alfa AF: 0.503 Hom.: 39062

Bravo AF: 0.421

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2425637; hg19: chr20-43024049;