5-83490080-A-G

Position:

• chr5-83490080-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004385.5(VCAN):​c.71-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,612,998 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (8 hom.)
• Consequence: VCAN NM_004385.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.225

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-83490080-A-G is Benign according to our data. Variant chr5-83490080-A-G is described in ClinVar as [Benign]. Clinvar id is 1166002.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-83490080-A-G is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 254 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCAN	NM_004385.5	c.71-18A>G		intron_variant		ENST00000265077.8	NP_004376.2
VCAN	NM_001164097.2	c.71-18A>G		intron_variant			NP_001157569.1
VCAN	NM_001164098.2	c.71-18A>G		intron_variant			NP_001157570.1
VCAN	NM_001126336.3	c.71-18A>G		intron_variant			NP_001119808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCAN	ENST00000265077.8	c.71-18A>G		intron_variant		1	NM_004385.5	ENSP00000265077.3

Frequencies

GnomAD3 genomes AF: 0.00167 AC: 254 AN: 151946 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00293

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00293

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00203 AC: 500 AN: 246434 Hom.: 1 AF XY: 0.00184 AC XY: 247 AN XY: 134376

Gnomad AFR exome AF: 0.000733

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00194

Gnomad NFE exome AF: 0.00394

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00288 AC: 4211 AN: 1460934 Hom.: 8 Cov.: 30 AF XY: 0.00269 AC XY: 1954 AN XY: 726756

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00232

Gnomad4 NFE exome AF: 0.00356

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome AF: 0.00167 AC: 254 AN: 152064 Hom.: 1 Cov.: 32 AF XY: 0.00159 AC XY: 118 AN XY: 74346

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00293

Gnomad4 NFE AF: 0.00293

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00186 Hom.: 0

Bravo AF: 0.00138

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.054
DANN	Benign	0.55

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: rs143037679; hg19: chr5-82785899;