chr5-83514895-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004385.5(VCAN):​c.1042+2499A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,146 control chromosomes in the GnomAD database, including 10,589 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 0.37 ( 10589 hom., cov: 33)

Consequence

VCAN
NM_004385.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

Publications

7 publications found
Variant links:
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 Gene-Disease associations (from GenCC):
  • Wagner disease
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VCANNM_004385.5 linkc.1042+2499A>G intron_variant Intron 6 of 14 ENST00000265077.8 NP_004376.2 P13611-1A0A024RAQ9Q59FG9
VCANNM_001164097.2 linkc.1042+2499A>G intron_variant Intron 6 of 13 NP_001157569.1 P13611-2A0A024RAL1Q6MZK8
VCANNM_001164098.2 linkc.1042+2499A>G intron_variant Intron 6 of 13 NP_001157570.1 P13611-3A0A024RAP3
VCANNM_001126336.3 linkc.1042+2499A>G intron_variant Intron 6 of 12 NP_001119808.1 P13611-4Q86W61

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VCANENST00000265077.8 linkc.1042+2499A>G intron_variant Intron 6 of 14 1 NM_004385.5 ENSP00000265077.3 P13611-1

Frequencies

GnomAD3 genomes
AF:
0.366
AC:
55709
AN:
152028
Hom.:
10585
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.388
Gnomad AMI
AF:
0.373
Gnomad AMR
AF:
0.449
Gnomad ASJ
AF:
0.437
Gnomad EAS
AF:
0.574
Gnomad SAS
AF:
0.426
Gnomad FIN
AF:
0.313
Gnomad MID
AF:
0.468
Gnomad NFE
AF:
0.318
Gnomad OTH
AF:
0.390
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.366
AC:
55742
AN:
152146
Hom.:
10589
Cov.:
33
AF XY:
0.370
AC XY:
27526
AN XY:
74392
show subpopulations
African (AFR)
AF:
0.388
AC:
16087
AN:
41504
American (AMR)
AF:
0.449
AC:
6868
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.437
AC:
1515
AN:
3464
East Asian (EAS)
AF:
0.574
AC:
2964
AN:
5160
South Asian (SAS)
AF:
0.426
AC:
2051
AN:
4818
European-Finnish (FIN)
AF:
0.313
AC:
3315
AN:
10584
Middle Eastern (MID)
AF:
0.462
AC:
135
AN:
292
European-Non Finnish (NFE)
AF:
0.318
AC:
21636
AN:
68002
Other (OTH)
AF:
0.393
AC:
831
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1800
3600
5401
7201
9001
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
550
1100
1650
2200
2750
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.349
Hom.:
28643
Bravo
AF:
0.380
Asia WGS
AF:
0.489
AC:
1704
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
13
DANN
Benign
0.70
PhyloP100
1.7
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

Publications

Other links and lift over

dbSNP: rs160380; hg19: chr5-82810714; API