5-83567100-G-A

Variant names:

• chr5-83567100-G-A
• rs160280
• NM_004385.5:c.9736-5316G>A

Variant summary

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

The NM_004385.5(VCAN):​c.9736-5316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,946 control chromosomes in the GnomAD database, including 4,245 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 0.23 (4245 hom., cov: 32)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• 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-AS1 (HGNC:40163): (VCAN antisense RNA 1)

LOC124901021 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (AMR) 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.9736-5316G>A		intron	N/A	NP_004376.2
	VCAN	NM_001164097.2		c.6775-5316G>A		intron	N/A	NP_001157569.1	P13611-2
	VCAN	NM_001164098.2		c.4474-5316G>A		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.9736-5316G>A		intron	N/A	ENSP00000265077.3	P13611-1
	VCAN	ENST00000343200.9	TSL:1	c.6775-5316G>A		intron	N/A	ENSP00000340062.5	P13611-2
	VCAN	ENST00000342785.8	TSL:1	c.4474-5316G>A		intron	N/A	ENSP00000342768.4	P13611-3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34355 AN: 151828 Hom.: 4241 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.226 AC: 34363 AN: 151946 Hom.: 4245 Cov.: 32 AF XY: 0.230 AC XY: 17081 AN XY: 74262

African (AFR) AF: 0.134 AC: 5543 AN: 41430

American (AMR) AF: 0.326 AC: 4981 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3468

East Asian (EAS) AF: 0.311 AC: 1605 AN: 5164

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4818

European-Finnish (FIN) AF: 0.276 AC: 2907 AN: 10534

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16307 AN: 67962

Other (OTH) AF: 0.261 AC: 551 AN: 2110

Alfa AF: 0.239 Hom.: 772

Bravo AF: 0.230

Asia WGS AF: 0.218 AC: 756 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.51
PhyloP100		1.7
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: rs160280; hg19: chr5-82862919; COSMIC: COSV54101202; COSMIC: COSV54101202;