5-83548909-T-C

Position:

• chr5-83548909-T-C

Variant summary

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

The NM_004385.5(VCAN):​c.9493+825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,192 control chromosomes in the GnomAD database, including 49,818 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 0.81 (49818 hom., cov: 33)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAN	NM_004385.5	c.9493+825T>C		intron_variant		ENST00000265077.8
VCAN-AS1	NR_136215.1	n.284+13122A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAN	ENST00000265077.8	c.9493+825T>C		intron_variant		1	NM_004385.5
VCAN-AS1	ENST00000513899.1	n.229-7208A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122475 AN: 152074 Hom.: 49758 Cov.: 33

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.813

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

GnomAD4 genome AF: 0.806 AC: 122595 AN: 152192 Hom.: 49818 Cov.: 33 AF XY: 0.798 AC XY: 59348 AN XY: 74392

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.812

Alfa AF: 0.792 Hom.: 98873

Bravo AF: 0.820

Asia WGS AF: 0.619 AC: 2153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.46

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: rs309596; hg19: chr5-82844728;