rs309578

Variant names:

• chr5-83578730-G-A
• rs309578
• NM_004385.5:c.9881-1250G>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.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
• Publications: 1 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=-0.89).
• 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 rank	MANE	Protein	UniProt
VCAN	NM_004385.5	c.9881-1250G>A		intron_variant	Intron 13 of 14	ENST00000265077.8	NP_004376.2
VCAN	NM_001164097.2	c.6920-1250G>A		intron_variant	Intron 12 of 13		NP_001157569.1
VCAN	NM_001164098.2	c.4619-1250G>A		intron_variant	Intron 12 of 13		NP_001157570.1
VCAN	NM_001126336.3	c.1658-1250G>A		intron_variant	Intron 11 of 12		NP_001119808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8	c.9881-1250G>A		intron_variant	Intron 13 of 14	1	NM_004385.5	ENSP00000265077.3

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

African (AFR) AF: 0.207 AC: 8574 AN: 41450

American (AMR) AF: 0.418 AC: 6379 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1904 AN: 5160

South Asian (SAS) AF: 0.379 AC: 1824 AN: 4816

European-Finnish (FIN) AF: 0.382 AC: 4023 AN: 10526

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23902 AN: 67950

Other (OTH) AF: 0.350 AC: 739 AN: 2112

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
PhyloP100		0.57
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: rs309578; hg19: chr5-82874549; COSMIC: COSV54101250;