rs717248

chr20-44396965-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.50-9093T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 152,154 control chromosomes in the GnomAD database, including 738 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 0.077 (738 hom., cov: 32)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF4A	NM_175914.5	c.50-9093T>C		intron_variant		ENST00000316673.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF4A	ENST00000316673.9	c.50-9093T>C		intron_variant		1	NM_175914.5
HNF4A	ENST00000457232.5	c.50-9093T>C		intron_variant		1
HNF4A	ENST00000609262.5	c.40+6286T>C		intron_variant		1
HNF4A	ENST00000609795.5	c.50-9093T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11758 AN: 152038 Hom.: 740 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.0622

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

GnomAD4 genome AF: 0.0773 AC: 11764 AN: 152154 Hom.: 738 Cov.: 32 AF XY: 0.0758 AC XY: 5640 AN XY: 74406

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0452

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.0413

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0483 Hom.: 353

Bravo AF: 0.0808

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.2
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: rs717248; hg19: chr20-43025605;