5-83509605-C-T

Position:

• chr5-83509605-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCAN	NM_004385.5	c.749-2498C>T		intron_variant		ENST00000265077.8	NP_004376.2
VCAN	NM_001164097.2	c.749-2498C>T		intron_variant			NP_001157569.1
VCAN	NM_001164098.2	c.749-2498C>T		intron_variant			NP_001157570.1
VCAN	NM_001126336.3	c.749-2498C>T		intron_variant			NP_001119808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8	c.749-2498C>T		intron_variant		1	NM_004385.5	ENSP00000265077.3

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

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.209

Alfa AF: 0.184 Hom.: 5465

Bravo AF: 0.194

Asia WGS AF: 0.299 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.84
DANN	Benign	0.68

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: rs251124; hg19: chr5-82805424;