5-83515681-A-G

Variant names:

• chr5-83515681-A-G
• rs173686
• NM_004385.5:c.1042+3285A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004385.5(VCAN):​c.1042+3285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,096 control chromosomes in the GnomAD database, including 24,374 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 0.54 (24374 hom., cov: 33)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682
• Publications: 29 publications found

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]

VCAN Gene-Disease associations (from GenCC):

• Wagner disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004385.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	NM_004385.5	MANE Select	c.1042+3285A>G		intron	N/A	NP_004376.2
	VCAN	NM_001164097.2		c.1042+3285A>G		intron	N/A	NP_001157569.1
	VCAN	NM_001164098.2		c.1042+3285A>G		intron	N/A	NP_001157570.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	ENST00000265077.8	TSL:1 MANE Select	c.1042+3285A>G		intron	N/A	ENSP00000265077.3
	VCAN	ENST00000343200.9	TSL:1	c.1042+3285A>G		intron	N/A	ENSP00000340062.5
	VCAN	ENST00000342785.8	TSL:1	c.1042+3285A>G		intron	N/A	ENSP00000342768.4

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82082 AN: 151978 Hom.: 24322 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.540 AC: 82189 AN: 152096 Hom.: 24374 Cov.: 33 AF XY: 0.546 AC XY: 40568 AN XY: 74342

African (AFR) AF: 0.754 AC: 31280 AN: 41496

American (AMR) AF: 0.547 AC: 8361 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2181 AN: 3470

East Asian (EAS) AF: 0.864 AC: 4455 AN: 5156

South Asian (SAS) AF: 0.519 AC: 2496 AN: 4812

European-Finnish (FIN) AF: 0.463 AC: 4892 AN: 10576

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26702 AN: 67974

Other (OTH) AF: 0.561 AC: 1185 AN: 2114

Alfa AF: 0.451 Hom.: 63842

Bravo AF: 0.559

Asia WGS AF: 0.675 AC: 2343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.8
DANN	Benign	0.63
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs173686; hg19: chr5-82811500; COSMIC: COSV54100778; COSMIC: COSV54100778;