rs11887

chrX-155239176-T-CchrX-155239176-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003372.7(VBP1):c.*334T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 145,308 control chromosomes in the GnomAD database, including 21,520 homozygotes. There are 22,804 hemizygotes in GnomAD. 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 0.55 (14276 hom., 18165 hem., cov: 23)
  • Exomes 𝑓: 0.71 (7244 hom. 4639 hem.)
• Consequence: VBP1 NM_003372.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498

Genes affected

VBP1 (HGNC:12662): (VHL binding protein 1) The protein encoded by this gene interacts with the Von Hippel-Lindau protein to form an intracellular complex. The encoded protein functions as a chaperone protein, and may play a role in the transport of the Von Hippel-Lindau protein from the perinuclear granules to the nucleus or cytoplasm. Alternative splicing and the use of alternate transcription start sites results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VBP1	NM_003372.7	c.*334T>C		3_prime_UTR_variant	6/6	ENST00000286428.7
VBP1	NM_001303543.1	c.*334T>C		3_prime_UTR_variant	6/6
VBP1	NM_001303544.1	c.*334T>C		3_prime_UTR_variant	7/7
VBP1	NM_001303545.1	c.*334T>C		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VBP1	ENST00000286428.7	c.*334T>C		3_prime_UTR_variant	6/6	1	NM_003372.7	P1
VBP1	ENST00000625964.2	c.*334T>C		3_prime_UTR_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.546 AC: 60404 AN: 110688 Hom.: 14280 Cov.: 23 AF XY: 0.552 AC XY: 18154 AN XY: 32908

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.713 AC: 24644 AN: 34569 Hom.: 7244 Cov.: 0 AF XY: 0.743 AC XY: 4639 AN XY: 6241

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.616

Gnomad4 ASJ exome AF: 0.718

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.735

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.545 AC: 60397 AN: 110739 Hom.: 14276 Cov.: 23 AF XY: 0.551 AC XY: 18165 AN XY: 32969

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.577

Alfa AF: 0.680 Hom.: 40237

Bravo AF: 0.521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11887; hg19: chrX-154467457;