rs2941484

Variant names:

• chr8-75566533-C-T
• rs2941484
• NM_004133.5:c.*2437C>T

Variant summary

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

The NM_004133.5(HNF4G):​c.*2437C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,240 control chromosomes in the GnomAD database, including 21,026 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 0.51 (20977 hom., cov: 32)
  • Exomes 𝑓: 0.47 (49 hom.)
• Consequence: HNF4G NM_004133.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• Publications: 40 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=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF4G	NM_004133.5	c.*2437C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000396423.4	NP_004124.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF4G	ENST00000396423.4	c.*2437C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_004133.5	ENSP00000379701.3
HNF4G	ENST00000674002.1	c.*2437C>T		3_prime_UTR_variant	Exon 10 of 10			ENSP00000501146.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77225 AN: 151690 Hom.: 20954 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.475 AC: 205 AN: 432 Hom.: 49 Cov.: 0 AF XY: 0.492 AC XY: 128 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.479 AC: 204 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.509 AC: 77295 AN: 151808 Hom.: 20977 Cov.: 32 AF XY: 0.504 AC XY: 37427 AN XY: 74202

African (AFR) AF: 0.715 AC: 29630 AN: 41460

American (AMR) AF: 0.377 AC: 5748 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1496 AN: 3464

East Asian (EAS) AF: 0.348 AC: 1802 AN: 5172

South Asian (SAS) AF: 0.411 AC: 1984 AN: 4824

European-Finnish (FIN) AF: 0.475 AC: 4936 AN: 10398

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30081 AN: 67922

Other (OTH) AF: 0.493 AC: 1042 AN: 2114

Alfa AF: 0.462 Hom.: 46265

Bravo AF: 0.507

Asia WGS AF: 0.387 AC: 1334 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.9
DANN	Benign	0.47
PhyloP100		-0.65
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: rs2941484; hg19: chr8-76478768;