rs6017341

Positions:

• chr20-44434646-C-G
• chr20-44434646-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The variant allele was found at a frequency of 0.0749 in 152,220 control chromosomes in the GnomAD database, including 655 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 0.075 (655 hom., cov: 30)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.72

Genes affected

(HGNC:):

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.44434646C>G		intergenic_region
HNF4A	NM_001258355.2	c.*4981C>G		downstream_gene_variant			NP_001245284.1
HNF4A	NM_178849.3	c.*4981C>G		downstream_gene_variant			NP_849180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11382 AN: 152010 Hom.: 654 Cov.: 30

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.00905

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0721

GnomAD4 exome AF: 0.0109 AC: 1 AN: 92 Hom.: 0 Cov.: 0 AF XY: 0.0161 AC XY: 1 AN XY: 62

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0749 AC: 11400 AN: 152128 Hom.: 655 Cov.: 30 AF XY: 0.0714 AC XY: 5309 AN XY: 74374

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.00888

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.0366

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0188 Hom.: 14

Bravo AF: 0.0874

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6017341; hg19: chr20-43063286;