8-75440343-A-C

Variant names:

• chr8-75440343-A-C
• rs830772
• ENST00000354370.5:c.-144+32181A>C

Variant summary

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

The ENST00000354370.5(HNF4G):​c.-144+32181A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,154 control chromosomes in the GnomAD database, including 54,334 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 0.84 (54334 hom., cov: 32)
• Consequence: HNF4G ENST00000354370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 4 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]

ENSG00000309942 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 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.-176+32379A>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.-144+32181A>C		intron	N/A	ENSP00000346339.1
	HNF4G	ENST00000396419.5	TSL:3	n.23+32379A>C		intron	N/A
	HNF4G	ENST00000494318.5	TSL:3	n.51+32379A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127610 AN: 152038 Hom.: 54287 Cov.: 32

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.839 AC: 127709 AN: 152154 Hom.: 54334 Cov.: 32 AF XY: 0.834 AC XY: 62028 AN XY: 74376

African (AFR) AF: 0.964 AC: 40059 AN: 41556

American (AMR) AF: 0.694 AC: 10602 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2902 AN: 3470

East Asian (EAS) AF: 0.648 AC: 3346 AN: 5164

South Asian (SAS) AF: 0.724 AC: 3499 AN: 4830

European-Finnish (FIN) AF: 0.834 AC: 8826 AN: 10580

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55681 AN: 67974

Other (OTH) AF: 0.852 AC: 1796 AN: 2108

Alfa AF: 0.825 Hom.: 23044

Bravo AF: 0.836

Asia WGS AF: 0.701 AC: 2437 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.0
DANN	Benign	0.67
PhyloP100		-0.30
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: rs830772; hg19: chr8-76352578;