rs6130608

chr20-44395368-T-C

Variant summary

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

The NM_175914.5(HNF4A):c.50-10690T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,340 control chromosomes in the GnomAD database, including 8,706 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 0.33 (8700 hom., cov: 34)
  • Exomes 𝑓: 0.25 (6 hom.)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

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 (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF4A	NM_175914.5	c.50-10690T>C		intron_variant		ENST00000316673.9
HNF4A-AS1	NR_172878.1	n.210+85A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-10690T>C		intron_variant		1	NM_175914.5
HNF4A-AS1	ENST00000452481.1	n.254+85A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49720 AN: 152108 Hom.: 8692 Cov.: 34

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.254 AC: 29 AN: 114 Hom.: 6 AF XY: 0.256 AC XY: 21 AN XY: 82

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.327 AC: 49754 AN: 152226 Hom.: 8700 Cov.: 34 AF XY: 0.328 AC XY: 24386 AN XY: 74436

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.313

Alfa AF: 0.298 Hom.: 3999

Bravo AF: 0.323

Asia WGS AF: 0.355 AC: 1235 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	6.1
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6130608; hg19: chr20-43024008;