5-83539126-C-T

Variant names:

• chr5-83539126-C-T
• rs113659987
• NM_004385.5:c.6123C>T

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.6123C>T​(p.Ile2041Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,613,890 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (38 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (49 hom.)
• Consequence: VCAN NM_004385.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.515
• Publications: 2 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=-0.74).
• BP6: Variant 5-83539126-C-T is Benign according to our data. Variant chr5-83539126-C-T is described in ClinVar as Benign. ClinVar VariationId is 259371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.515 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1809/152192) while in subpopulation AFR AF = 0.0412 (1712/41508). AF 95% confidence interval is 0.0396. There are 38 homozygotes in GnomAd4. There are 862 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1809 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.6123C>T	p.Ile2041Ile	synonymous	Exon 8 of 15	NP_004376.2
	VCAN	NM_001164097.2		c.3162C>T	p.Ile1054Ile	synonymous	Exon 7 of 14	NP_001157569.1	P13611-2
	VCAN	NM_001164098.2		c.4004-6411C>T		intron	N/A	NP_001157570.1	P13611-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAN	ENST00000265077.8	TSL:1 MANE Select	c.6123C>T	p.Ile2041Ile	synonymous	Exon 8 of 15	ENSP00000265077.3	P13611-1
	VCAN	ENST00000343200.9	TSL:1	c.3162C>T	p.Ile1054Ile	synonymous	Exon 7 of 14	ENSP00000340062.5	P13611-2
	VCAN	ENST00000513960.5	TSL:1	c.3162C>T	p.Ile1054Ile	synonymous	Exon 7 of 7	ENSP00000426251.1	D6RGZ6

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1796 AN: 152074 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.00291 AC: 730 AN: 250562 AF XY: 0.00219

Gnomad AFR exome AF: 0.0411

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00128 AC: 1865 AN: 1461698 Hom.: 49 Cov.: 79 AF XY: 0.00114 AC XY: 826 AN XY: 727144

African (AFR) AF: 0.0448 AC: 1500 AN: 33476

American (AMR) AF: 0.00193 AC: 86 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39666

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000648 AC: 72 AN: 1111962

Other (OTH) AF: 0.00306 AC: 185 AN: 60390

GnomAD4 genome AF: 0.0119 AC: 1809 AN: 152192 Hom.: 38 Cov.: 32 AF XY: 0.0116 AC XY: 862 AN XY: 74418

African (AFR) AF: 0.0412 AC: 1712 AN: 41508

American (AMR) AF: 0.00517 AC: 79 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68002

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00560 Hom.: 7

Bravo AF: 0.0143

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

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	-0.74
CADD	Benign	3.4
DANN	Benign	0.52
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism

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: rs113659987; hg19: chr5-82834945;