rs1805100

Positions:

• chr8-75564161-G-A
• chr8-75564161-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000396423.4(HNF4G):​c.*65G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,562,848 control chromosomes in the GnomAD database, including 185,180 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 0.53 (22910 hom., cov: 33)
  • Exomes 𝑓: 0.48 (162270 hom.)
• Consequence: HNF4G ENST00000396423.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF4G	NM_004133.5	c.*65G>A		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.*65G>A		3_prime_UTR_variant	10/10	1	NM_004133.5	ENSP00000379701
HNF4G	ENST00000354370.5	c.*65G>A		3_prime_UTR_variant	11/11	1		ENSP00000346339	P1
HNF4G	ENST00000674002.1	c.*65G>A		3_prime_UTR_variant	10/10			ENSP00000501146

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81300 AN: 152010 Hom.: 22887 Cov.: 33

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.475 AC: 670265 AN: 1410720 Hom.: 162270 Cov.: 21 AF XY: 0.474 AC XY: 332673 AN XY: 702458

Gnomad4 AFR exome AF: 0.729

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.535 AC: 81370 AN: 152128 Hom.: 22910 Cov.: 33 AF XY: 0.532 AC XY: 39526 AN XY: 74360

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.511

Alfa AF: 0.480 Hom.: 24017

Bravo AF: 0.527

Asia WGS AF: 0.395 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.87

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: rs1805100; hg19: chr8-76476396; COSMIC: COSV62966601;