rs17348129

Variant names:

• chr5-83530949-A-G
• rs17348129
• NM_004385.5:c.4004-6058A>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.4004-6058A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,046 control chromosomes in the GnomAD database, including 1,686 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 0.14 (1686 hom., cov: 32)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5	c.4004-6058A>G		intron_variant	Intron 7 of 14	ENST00000265077.8	NP_004376.2
VCAN	NM_001164097.2	c.1043-6058A>G		intron_variant	Intron 6 of 13		NP_001157569.1
VCAN	NM_001164098.2	c.4003+8640A>G		intron_variant	Intron 7 of 13		NP_001157570.1
VCAN	NM_001126336.3	c.1043-14588A>G		intron_variant	Intron 6 of 12		NP_001119808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8	c.4004-6058A>G		intron_variant	Intron 7 of 14	1	NM_004385.5	ENSP00000265077.3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21310 AN: 151928 Hom.: 1686 Cov.: 32

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0711

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.140 AC: 21305 AN: 152046 Hom.: 1686 Cov.: 32 AF XY: 0.140 AC XY: 10375 AN XY: 74336

African (AFR) AF: 0.0718 AC: 2980 AN: 41504

American (AMR) AF: 0.133 AC: 2034 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 806 AN: 3466

East Asian (EAS) AF: 0.0707 AC: 365 AN: 5166

South Asian (SAS) AF: 0.178 AC: 860 AN: 4830

European-Finnish (FIN) AF: 0.163 AC: 1724 AN: 10576

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11957 AN: 67948

Other (OTH) AF: 0.166 AC: 350 AN: 2108

Alfa AF: 0.153 Hom.: 910

Bravo AF: 0.134

Asia WGS AF: 0.124 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.63
PhyloP100		-0.16
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: rs17348129; hg19: chr5-82826768;