rs6093976

Positions:

• chr20-44407140-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000316673.9(HNF4A):​c.225-241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,202 control chromosomes in the GnomAD database, including 1,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.13 (1641 hom., cov: 32)
• Consequence: HNF4A ENST00000316673.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.944

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 20-44407140-C-T is Benign according to our data. Variant chr20-44407140-C-T is described in ClinVar as [Benign]. Clinvar id is 1235855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.225-241C>T		intron_variant		ENST00000316673.9	NP_787110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.225-241C>T		intron_variant		1	NM_175914.5	ENSP00000315180

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19693 AN: 152084 Hom.: 1639 Cov.: 32

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.129 AC: 19693 AN: 152202 Hom.: 1641 Cov.: 32 AF XY: 0.130 AC XY: 9652 AN XY: 74422

Gnomad4 AFR AF: 0.0319

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.152

Alfa AF: 0.165 Hom.: 1092

Bravo AF: 0.123

Asia WGS AF: 0.191 AC: 666 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.50
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6093976; hg19: chr20-43035780;