chr8-75505702-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000354370.5(HNF4G):​c.-24+15494A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF4G	NM_001330561.2	c.-24+15494A>C		intron_variant	Intron 3 of 11		NP_001317490.1
HNF4G	XM_017013373.2	c.-24+15494A>C		intron_variant	Intron 4 of 12		XP_016868862.1
HNF4G	XM_017013374.2	c.-24+15494A>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+15494A>C		intron_variant	Intron 2 of 10	1		ENSP00000346339.1
HNF4G	ENST00000396419.5	n.143+15494A>C		intron_variant	Intron 2 of 4	3
HNF4G	ENST00000494318.5	n.295+10206A>C		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.060
DANN	Benign	0.52
PhyloP100		-1.3

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;