rs309578

chr5-83578730-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004385.5(VCAN):c.9881-1250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,964 control chromosomes in the GnomAD database, including 8,438 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 0.32 (8438 hom., cov: 32)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAN	NM_004385.5	c.9881-1250G>A		intron_variant		ENST00000265077.8
VCAN	NM_001126336.3	c.1658-1250G>A		intron_variant
VCAN	NM_001164097.2	c.6920-1250G>A		intron_variant
VCAN	NM_001164098.2	c.4619-1250G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAN	ENST00000265077.8	c.9881-1250G>A		intron_variant		1	NM_004385.5
VCAN-AS1	ENST00000513899.1	n.228+2363C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49108 AN: 151848 Hom.: 8435 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.323 AC: 49125 AN: 151964 Hom.: 8438 Cov.: 32 AF XY: 0.329 AC XY: 24414 AN XY: 74256

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.350

Alfa AF: 0.327 Hom.: 1039

Bravo AF: 0.320

Asia WGS AF: 0.343 AC: 1183 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.1
Dann	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs309578; hg19: chr5-82874549; COSMIC: COSV54101250;