8-75504626-T-C

Variant names:

• chr8-75504626-T-C
• rs2612300
• ENST00000354370.5:c.-24+14418T>C

Variant summary

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

The ENST00000354370.5(HNF4G):​c.-24+14418T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,102 control chromosomes in the GnomAD database, including 6,515 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 0.28 (6515 hom., cov: 32)
• Consequence: HNF4G ENST00000354370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• 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=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354370.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF4G	NM_001330561.2		c.-24+14418T>C		intron	N/A	NP_001317490.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF4G	ENST00000354370.5	TSL:1	c.-24+14418T>C		intron	N/A	ENSP00000346339.1
	HNF4G	ENST00000396419.5	TSL:3	n.143+14418T>C		intron	N/A
	HNF4G	ENST00000494318.5	TSL:3	n.295+9130T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42222 AN: 151984 Hom.: 6526 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.277 AC: 42200 AN: 152102 Hom.: 6515 Cov.: 32 AF XY: 0.272 AC XY: 20256 AN XY: 74350

African (AFR) AF: 0.155 AC: 6429 AN: 41522

American (AMR) AF: 0.276 AC: 4218 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1476 AN: 3466

East Asian (EAS) AF: 0.238 AC: 1230 AN: 5162

South Asian (SAS) AF: 0.224 AC: 1082 AN: 4828

European-Finnish (FIN) AF: 0.288 AC: 3050 AN: 10580

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23675 AN: 67954

Other (OTH) AF: 0.331 AC: 699 AN: 2110

Alfa AF: 0.315 Hom.: 5073

Bravo AF: 0.275

Asia WGS AF: 0.232 AC: 804 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		0.32
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: rs2612300; hg19: chr8-76416861;