rs779808

Positions:

• chr3-10143337-C-T

Variant summary

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

The NM_000551.4(VHL):​c.340+1150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 151,910 control chromosomes in the GnomAD database, including 27,799 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 0.57 (27799 hom., cov: 32)
• Consequence: VHL NM_000551.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

Genes affected

VHL (HGNC:12687): (von Hippel-Lindau tumor suppressor) This gene encodes a component of a ubiquitination complex. The encoded protein is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. In addition to oxygen-related gene expression, this protein plays a role in many other cellular processes including cilia formation, cytokine signaling, regulation of senescence, and formation of the extracellular matrix. Variants of this gene are associated with von Hippel-Lindau syndrome, pheochromocytoma, erythrocytosis, renal cell carcinoma, and cerebellar hemangioblastoma. [provided by RefSeq, Jun 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VHL	NM_000551.4	c.340+1150C>T		intron_variant		ENST00000256474.3	NP_000542.1
VHL	NM_001354723.2	c.*17+316C>T		intron_variant			NP_001341652.1
VHL	NM_198156.3	c.340+1150C>T		intron_variant			NP_937799.1
VHL	NR_176335.1	n.669+316C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VHL	ENST00000256474.3	c.340+1150C>T		intron_variant		1	NM_000551.4	ENSP00000256474	P1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86477 AN: 151792 Hom.: 27785 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.606

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.570 AC: 86519 AN: 151910 Hom.: 27799 Cov.: 32 AF XY: 0.577 AC XY: 42855 AN XY: 74248

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.599

Alfa AF: 0.624 Hom.: 3945

Bravo AF: 0.548

Asia WGS AF: 0.654 AC: 2274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.8
DANN	Benign	0.96

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: rs779808; hg19: chr3-10185021;