5-83509605-C-T

Variant names:

• chr5-83509605-C-T
• rs251124
• NM_004385.5:c.749-2498C>T

Variant summary

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

The NM_004385.5(VCAN):​c.749-2498C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,092 control chromosomes in the GnomAD database, including 3,202 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 0.20 (3202 hom., cov: 32)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 25 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: G2P, Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	NM_004385.5	MANE Select	c.749-2498C>T		intron	N/A	NP_004376.2
	VCAN	NM_001164097.2		c.749-2498C>T		intron	N/A	NP_001157569.1	P13611-2
	VCAN	NM_001164098.2		c.749-2498C>T		intron	N/A	NP_001157570.1	P13611-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	ENST00000265077.8	TSL:1 MANE Select	c.749-2498C>T		intron	N/A	ENSP00000265077.3	P13611-1
	VCAN	ENST00000343200.9	TSL:1	c.749-2498C>T		intron	N/A	ENSP00000340062.5	P13611-2
	VCAN	ENST00000342785.8	TSL:1	c.749-2498C>T		intron	N/A	ENSP00000342768.4	P13611-3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30040 AN: 151974 Hom.: 3204 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.198 AC: 30049 AN: 152092 Hom.: 3202 Cov.: 32 AF XY: 0.204 AC XY: 15181 AN XY: 74354

African (AFR) AF: 0.175 AC: 7246 AN: 41480

American (AMR) AF: 0.201 AC: 3075 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1718 AN: 5180

South Asian (SAS) AF: 0.290 AC: 1397 AN: 4814

European-Finnish (FIN) AF: 0.262 AC: 2772 AN: 10574

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12112 AN: 67984

Other (OTH) AF: 0.209 AC: 442 AN: 2114

Alfa AF: 0.184 Hom.: 8636

Bravo AF: 0.194

Asia WGS AF: 0.299 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.84
DANN	Benign	0.68
PhyloP100		-0.15
Mutation Taster		=99/1	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: rs251124; hg19: chr5-82805424;