8-75458633-T-G

Variant names:

• chr8-75458633-T-G
• rs2056089
• ENST00000354370.5:c.-143-31456T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000354370.5(HNF4G):​c.-143-31456T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,218 control chromosomes in the GnomAD database, including 273 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 0.050 (273 hom., cov: 31)
• Consequence: HNF4G ENST00000354370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416
• Publications: 1 publications found

Genes affected

HNF4G (HGNC:5026): (hepatocyte nuclear factor 4 gamma) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in several cellular components, including intercellular bridge; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF4G	NM_001330561.2	c.-175-27152T>G		intron_variant	Intron 1 of 11		NP_001317490.1
HNF4G	XM_017013373.2	c.-253-22773T>G		intron_variant	Intron 1 of 12		XP_016868862.1
HNF4G	XM_017013374.2	c.-143-31456T>G		intron_variant	Intron 1 of 10		XP_016868863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF4G	ENST00000354370.5	c.-143-31456T>G		intron_variant	Intron 1 of 10	1		ENSP00000346339.1
HNF4G	ENST00000396419.5	n.24-31456T>G		intron_variant	Intron 1 of 4	3
HNF4G	ENST00000494318.5	n.52-27152T>G		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7586 AN: 152098 Hom.: 273 Cov.: 31

Gnomad AFR AF: 0.0910

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0763

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.0376

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0499 AC: 7597 AN: 152218 Hom.: 273 Cov.: 31 AF XY: 0.0497 AC XY: 3699 AN XY: 74424

African (AFR) AF: 0.0909 AC: 3774 AN: 41522

American (AMR) AF: 0.0579 AC: 884 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0763 AC: 265 AN: 3472

East Asian (EAS) AF: 0.0356 AC: 184 AN: 5168

South Asian (SAS) AF: 0.0377 AC: 182 AN: 4832

European-Finnish (FIN) AF: 0.0230 AC: 244 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0288 AC: 1959 AN: 68020

Other (OTH) AF: 0.0445 AC: 94 AN: 2114

Alfa AF: 0.0331 Hom.: 260

Bravo AF: 0.0567

Asia WGS AF: 0.0410 AC: 142 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.7
DANN	Benign	0.71
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2056089; hg19: chr8-76370868;