5-83560700-C-T

Variant names:

• chr5-83560700-C-T
• rs309587
• NM_004385.5:c.9735+5662C>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.9735+5662C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,072 control chromosomes in the GnomAD database, including 36,530 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 0.69 (36530 hom., cov: 32)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 3 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAN	NM_004385.5	c.9735+5662C>T		intron_variant	Intron 12 of 14	ENST00000265077.8	NP_004376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8	c.9735+5662C>T		intron_variant	Intron 12 of 14	1	NM_004385.5	ENSP00000265077.3

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104565 AN: 151954 Hom.: 36489 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.688 AC: 104656 AN: 152072 Hom.: 36530 Cov.: 32 AF XY: 0.680 AC XY: 50524 AN XY: 74340

African (AFR) AF: 0.759 AC: 31481 AN: 41490

American (AMR) AF: 0.766 AC: 11699 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2490 AN: 3466

East Asian (EAS) AF: 0.492 AC: 2542 AN: 5166

South Asian (SAS) AF: 0.460 AC: 2218 AN: 4824

European-Finnish (FIN) AF: 0.606 AC: 6408 AN: 10580

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45555 AN: 67960

Other (OTH) AF: 0.695 AC: 1467 AN: 2110

Alfa AF: 0.689 Hom.: 44207

Bravo AF: 0.710

Asia WGS AF: 0.492 AC: 1711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.22
PhyloP100		-1.5
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: rs309587; hg19: chr5-82856519;