20-44399750-A-G

Position:

• chr20-44399750-A-G

Variant summary

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

The NM_175914.5(HNF4A):​c.50-6308A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,028 control chromosomes in the GnomAD database, including 3,545 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 0.20 (3545 hom., cov: 31)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF4A	NM_175914.5	c.50-6308A>G		intron_variant		ENST00000316673.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-6308A>G		intron_variant		1	NM_175914.5
HNF4A	ENST00000457232.5	c.50-6308A>G		intron_variant		1
HNF4A	ENST00000609262.5	c.41-6308A>G		intron_variant		1
HNF4A	ENST00000609795.5	c.50-6308A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30277 AN: 151910 Hom.: 3541 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.199 AC: 30285 AN: 152028 Hom.: 3545 Cov.: 31 AF XY: 0.199 AC XY: 14821 AN XY: 74346

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.211

Alfa AF: 0.149 Hom.: 1780

Bravo AF: 0.204

Asia WGS AF: 0.237 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.87
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3212172; hg19: chr20-43028390;