rs2652106

chr5-83498217-G-T

Variant summary

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

The NM_004385.5(VCAN):c.748+4286G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,888 control chromosomes in the GnomAD database, including 12,509 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 0.39 (12509 hom., cov: 32)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

Genes affected

VCAN (HGNC:2464): (versican) This gene is a member of the aggrecan/versican proteoglycan family. The protein encoded is a large chondroitin sulfate proteoglycan and is a major component of the extracellular matrix. This protein is involved in cell adhesion, proliferation, proliferation, migration and angiogenesis and plays a central role in tissue morphogenesis and maintenance. Mutations in this gene are the cause of Wagner syndrome type 1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAN	NM_004385.5	c.748+4286G>T		intron_variant		ENST00000265077.8
VCAN	NM_001126336.3	c.748+4286G>T		intron_variant
VCAN	NM_001164097.2	c.748+4286G>T		intron_variant
VCAN	NM_001164098.2	c.748+4286G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAN	ENST00000265077.8	c.748+4286G>T		intron_variant		1	NM_004385.5

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58779 AN: 151770 Hom.: 12473 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.387 AC: 58855 AN: 151888 Hom.: 12509 Cov.: 32 AF XY: 0.389 AC XY: 28879 AN XY: 74222

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.360

Alfa AF: 0.321 Hom.: 11461

Bravo AF: 0.392

Asia WGS AF: 0.426 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.29
Dann	Benign	0.30

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: rs2652106; hg19: chr5-82794036; COSMIC: COSV54100738;