chr8-75561823-A-G

Variant names:

• chr8-75561823-A-G
• rs1464093
• NM_004133.5:c.1246+1357A>G

Variant summary

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

The NM_004133.5(HNF4G):​c.1246+1357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,084 control chromosomes in the GnomAD database, including 2,758 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 0.18 (2758 hom., cov: 32)
• Consequence: HNF4G NM_004133.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF4G	NM_004133.5	c.1246+1357A>G		intron_variant	Intron 9 of 9	ENST00000396423.4	NP_004124.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF4G	ENST00000396423.4	c.1246+1357A>G		intron_variant	Intron 9 of 9	1	NM_004133.5	ENSP00000379701.3
HNF4G	ENST00000354370.5	c.1105+1357A>G		intron_variant	Intron 10 of 10	1		ENSP00000346339.1
HNF4G	ENST00000674002.1	c.1216+1357A>G		intron_variant	Intron 9 of 9			ENSP00000501146.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27968 AN: 151966 Hom.: 2759 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.184 AC: 27974 AN: 152084 Hom.: 2758 Cov.: 32 AF XY: 0.185 AC XY: 13791 AN XY: 74348

African (AFR) AF: 0.186 AC: 7704 AN: 41472

American (AMR) AF: 0.136 AC: 2079 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3472

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5184

South Asian (SAS) AF: 0.103 AC: 498 AN: 4826

European-Finnish (FIN) AF: 0.328 AC: 3461 AN: 10562

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13066 AN: 67986

Other (OTH) AF: 0.174 AC: 367 AN: 2112

Alfa AF: 0.182 Hom.: 10695

Bravo AF: 0.168

Asia WGS AF: 0.0770 AC: 267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.47
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1464093; hg19: chr8-76474058;