ENST00000354370.5:c.-24+14418T>C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF4G	NM_001330561.2	c.-24+14418T>C		intron_variant	Intron 3 of 11		NP_001317490.1
HNF4G	XM_017013373.2	c.-24+14418T>C		intron_variant	Intron 4 of 12		XP_016868862.1
HNF4G	XM_017013374.2	c.-24+14418T>C		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+14418T>C		intron_variant	Intron 2 of 10	1		ENSP00000346339.1
HNF4G	ENST00000396419.5	n.143+14418T>C		intron_variant	Intron 2 of 4	3
HNF4G	ENST00000494318.5	n.295+9130T>C		intron_variant	Intron 4 of 4	3

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

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.331

Alfa AF: 0.292 Hom.: 2166

Bravo AF: 0.275

Asia WGS AF: 0.232 AC: 804 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2612300; hg19: chr8-76416861;