rs2941484

Positions:

• chr8-75566533-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
HNF4G	NM_004133.5	c.*2437C>T		3_prime_UTR_variant	10/10	ENST00000396423.4	NP_004124.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF4G	ENST00000396423.4	c.*2437C>T		3_prime_UTR_variant	10/10	1	NM_004133.5	ENSP00000379701.3
HNF4G	ENST00000674002.1	c.*2437C>T		3_prime_UTR_variant	10/10			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

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

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

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.493

Alfa AF: 0.450 Hom.: 17244

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2941484; hg19: chr8-76478768;