chr20-44356715-A-G

Position:

• chr20-44356715-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.49+862A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,220 control chromosomes in the GnomAD database, including 2,760 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 0.19 (2760 hom., cov: 32)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF4A	NM_175914.5	c.49+862A>G		intron_variant		ENST00000316673.9
HNF4A-AS1	NR_172878.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF4A	ENST00000316673.9	c.49+862A>G		intron_variant		1	NM_175914.5
HNF4A	ENST00000457232.5	c.49+862A>G		intron_variant		1
HNF4A	ENST00000609262.5	c.-183+862A>G		intron_variant		1
HNF4A	ENST00000609795.5	c.49+862A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28260 AN: 152102 Hom.: 2761 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.186 AC: 28258 AN: 152220 Hom.: 2760 Cov.: 32 AF XY: 0.182 AC XY: 13572 AN XY: 74414

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.177

Alfa AF: 0.214 Hom.: 6221

Bravo AF: 0.182

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6031546; hg19: chr20-42985355;