rs16900528
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004385.5(VCAN):āc.4569A>Gā(p.Thr1523=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 1,613,190 control chromosomes in the GnomAD database, including 5,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.069 ( 448 hom., cov: 32)
Exomes š: 0.083 ( 5383 hom. )
Consequence
VCAN
NM_004385.5 synonymous
NM_004385.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.102
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 5-83537572-A-G is Benign according to our data. Variant chr5-83537572-A-G is described in ClinVar as [Benign]. Clinvar id is 259366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-83537572-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.102 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0882 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCAN | NM_004385.5 | c.4569A>G | p.Thr1523= | synonymous_variant | 8/15 | ENST00000265077.8 | |
VCAN-AS1 | NR_136215.1 | n.285-3399T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCAN | ENST00000265077.8 | c.4569A>G | p.Thr1523= | synonymous_variant | 8/15 | 1 | NM_004385.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0687 AC: 10448AN: 152112Hom.: 448 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
10448
AN:
152112
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0769 AC: 19217AN: 249858Hom.: 845 AF XY: 0.0789 AC XY: 10653AN XY: 135012
GnomAD3 exomes
AF:
AC:
19217
AN:
249858
Hom.:
AF XY:
AC XY:
10653
AN XY:
135012
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0834 AC: 121802AN: 1460960Hom.: 5383 Cov.: 72 AF XY: 0.0838 AC XY: 60878AN XY: 726792
GnomAD4 exome
AF:
AC:
121802
AN:
1460960
Hom.:
Cov.:
72
AF XY:
AC XY:
60878
AN XY:
726792
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0686 AC: 10450AN: 152230Hom.: 448 Cov.: 32 AF XY: 0.0700 AC XY: 5207AN XY: 74426
GnomAD4 genome
?
AF:
AC:
10450
AN:
152230
Hom.:
Cov.:
32
AF XY:
AC XY:
5207
AN XY:
74426
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
361
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Wagner syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Vitreoretinopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at