8-75505702-A-G

Variant names:

• chr8-75505702-A-G
• rs2943559
• ENST00000354370.5:c.-24+15494A>G

Variant summary

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

The ENST00000354370.5(HNF4G):​c.-24+15494A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,582 control chromosomes in the GnomAD database, including 1,327 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 0.11 (1327 hom., cov: 32)
• Consequence: HNF4G ENST00000354370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 58 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF4G	NM_001330561.2	c.-24+15494A>G		intron_variant	Intron 3 of 11		NP_001317490.1
HNF4G	XM_017013373.2	c.-24+15494A>G		intron_variant	Intron 4 of 12		XP_016868862.1
HNF4G	XM_017013374.2	c.-24+15494A>G		intron_variant	Intron 2 of 10		XP_016868863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF4G	ENST00000354370.5	c.-24+15494A>G		intron_variant	Intron 2 of 10	1		ENSP00000346339.1
HNF4G	ENST00000396419.5	n.143+15494A>G		intron_variant	Intron 2 of 4	3
HNF4G	ENST00000494318.5	n.295+10206A>G		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17300 AN: 151474 Hom.: 1322 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0886

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.0763

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.114 AC: 17340 AN: 151582 Hom.: 1327 Cov.: 32 AF XY: 0.110 AC XY: 8112 AN XY: 74072

African (AFR) AF: 0.221 AC: 9104 AN: 41272

American (AMR) AF: 0.0804 AC: 1225 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3470

East Asian (EAS) AF: 0.0890 AC: 459 AN: 5160

South Asian (SAS) AF: 0.0676 AC: 326 AN: 4822

European-Finnish (FIN) AF: 0.0311 AC: 325 AN: 10456

Middle Eastern (MID) AF: 0.114 AC: 33 AN: 290

European-Non Finnish (NFE) AF: 0.0763 AC: 5181 AN: 67862

Other (OTH) AF: 0.125 AC: 263 AN: 2108

Alfa AF: 0.0898 Hom.: 1918

Bravo AF: 0.125

Asia WGS AF: 0.0750 AC: 260 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.068
DANN	Benign	0.47
PhyloP100		-1.3
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: rs2943559; hg19: chr8-76417937;