rs830772

chr8-75440343-A-C

Variant summary

Our verdict is Benign. Variant got -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

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF4G	NM_001330561.2	c.-176+32379A>C		intron_variant
HNF4G	XM_017013373.2	c.-254+32379A>C		intron_variant
HNF4G	XM_017013374.2	c.-144+32379A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF4G	ENST00000354370.5	c.-144+32181A>C		intron_variant		1		P1
HNF4G	ENST00000396419.5	n.23+32379A>C		intron_variant, non_coding_transcript_variant		3
HNF4G	ENST00000494318.5	n.51+32379A>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.834

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.852

Alfa AF: 0.825 Hom.: 12602

Bravo AF: 0.836

Asia WGS AF: 0.701 AC: 2437 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	5.0
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs830772; hg19: chr8-76352578;