8-75551336-T-C

Variant names:

• chr8-75551336-T-C
• rs2272668
• NM_004133.5:c.383-52T>C

Variant summary

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

The NM_004133.5(HNF4G):​c.383-52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,014,188 control chromosomes in the GnomAD database, including 25,317 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 0.22 (3933 hom., cov: 31)
  • Exomes 𝑓: 0.22 (21384 hom.)
• Consequence: HNF4G NM_004133.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF4G	NM_004133.5	c.383-52T>C		intron_variant	Intron 3 of 9	ENST00000396423.4	NP_004124.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF4G	ENST00000396423.4	c.383-52T>C		intron_variant	Intron 3 of 9	1	NM_004133.5	ENSP00000379701.3
HNF4G	ENST00000354370.5	c.242-52T>C		intron_variant	Intron 4 of 10	1		ENSP00000346339.1
HNF4G	ENST00000674002.1	c.353-52T>C		intron_variant	Intron 3 of 9			ENSP00000501146.1
HNF4G	ENST00000396419.5	n.239-52T>C		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33826 AN: 151750 Hom.: 3936 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.215 AC: 185788 AN: 862318 Hom.: 21384 Cov.: 11 AF XY: 0.212 AC XY: 95482 AN XY: 450144

African (AFR) AF: 0.225 AC: 4758 AN: 21160

American (AMR) AF: 0.190 AC: 7360 AN: 38724

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 4842 AN: 21180

East Asian (EAS) AF: 0.117 AC: 4251 AN: 36294

South Asian (SAS) AF: 0.124 AC: 8456 AN: 67990

European-Finnish (FIN) AF: 0.339 AC: 17509 AN: 51622

Middle Eastern (MID) AF: 0.276 AC: 1225 AN: 4442

European-Non Finnish (NFE) AF: 0.221 AC: 128599 AN: 580782

Other (OTH) AF: 0.219 AC: 8788 AN: 40124

GnomAD4 genome AF: 0.223 AC: 33837 AN: 151870 Hom.: 3933 Cov.: 31 AF XY: 0.225 AC XY: 16661 AN XY: 74206

African (AFR) AF: 0.227 AC: 9415 AN: 41416

American (AMR) AF: 0.199 AC: 3040 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3464

East Asian (EAS) AF: 0.0962 AC: 496 AN: 5158

South Asian (SAS) AF: 0.122 AC: 588 AN: 4818

European-Finnish (FIN) AF: 0.357 AC: 3757 AN: 10522

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15046 AN: 67946

Other (OTH) AF: 0.226 AC: 475 AN: 2102

Alfa AF: 0.220 Hom.: 5533

Bravo AF: 0.213

Asia WGS AF: 0.143 AC: 497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.1
DANN	Benign	0.34
PhyloP100		0.021
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: rs2272668; hg19: chr8-76463571;