chr5-83542078-G-A

Variant names:

• chr5-83542078-G-A
• rs113014073
• NM_004385.5:c.9075G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004385.5(VCAN):​c.9075G>A​(p.Thr3025Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 1,613,704 control chromosomes in the GnomAD database, including 1,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (87 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1130 hom.)
• Consequence: VCAN NM_004385.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.307
• Publications: 7 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-83542078-G-A is Benign according to our data. Variant chr5-83542078-G-A is described in ClinVar as Benign. ClinVar VariationId is 259375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.307 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0276 (4203/152248) while in subpopulation NFE AF = 0.0387 (2635/68014). AF 95% confidence interval is 0.0375. There are 87 homozygotes in GnomAd4. There are 2020 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4203 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004385.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	NM_004385.5	MANE Select	c.9075G>A	p.Thr3025Thr	synonymous	Exon 8 of 15	NP_004376.2
	VCAN	NM_001164097.2		c.6114G>A	p.Thr2038Thr	synonymous	Exon 7 of 14	NP_001157569.1
	VCAN	NM_001164098.2		c.4004-3459G>A		intron	N/A	NP_001157570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	ENST00000265077.8	TSL:1 MANE Select	c.9075G>A	p.Thr3025Thr	synonymous	Exon 8 of 15	ENSP00000265077.3
	VCAN	ENST00000343200.9	TSL:1	c.6114G>A	p.Thr2038Thr	synonymous	Exon 7 of 14	ENSP00000340062.5
	VCAN	ENST00000342785.8	TSL:1	c.4004-3459G>A		intron	N/A	ENSP00000342768.4

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4207 AN: 152130 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.00702

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.0350

GnomAD2 exomes AF: 0.0305 AC: 7655 AN: 250712 AF XY: 0.0314

Gnomad AFR exome AF: 0.00628

Gnomad AMR exome AF: 0.0204

Gnomad ASJ exome AF: 0.0791

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0331

Gnomad NFE exome AF: 0.0412

Gnomad OTH exome AF: 0.0435

GnomAD4 exome AF: 0.0359 AC: 52450 AN: 1461456 Hom.: 1130 Cov.: 34 AF XY: 0.0356 AC XY: 25883 AN XY: 726960

African (AFR) AF: 0.00666 AC: 223 AN: 33470

American (AMR) AF: 0.0222 AC: 992 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0800 AC: 2090 AN: 26130

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39686

South Asian (SAS) AF: 0.0138 AC: 1192 AN: 86254

European-Finnish (FIN) AF: 0.0314 AC: 1677 AN: 53412

Middle Eastern (MID) AF: 0.0404 AC: 233 AN: 5764

European-Non Finnish (NFE) AF: 0.0395 AC: 43911 AN: 1111638

Other (OTH) AF: 0.0352 AC: 2126 AN: 60382

GnomAD4 genome AF: 0.0276 AC: 4203 AN: 152248 Hom.: 87 Cov.: 32 AF XY: 0.0271 AC XY: 2020 AN XY: 74450

African (AFR) AF: 0.00700 AC: 291 AN: 41562

American (AMR) AF: 0.0304 AC: 465 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0859 AC: 298 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4820

European-Finnish (FIN) AF: 0.0315 AC: 334 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0387 AC: 2635 AN: 68014

Other (OTH) AF: 0.0346 AC: 73 AN: 2108

Alfa AF: 0.0377 Hom.: 88

Bravo AF: 0.0265

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0444

EpiControl AF: 0.0445

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Wagner disease (2)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Vitreoretinopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.65
DANN	Benign	0.38
PhyloP100		0.31
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: rs113014073; hg19: chr5-82837897; COSMIC: COSV54117974; COSMIC: COSV54117974;