rs762594014
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_014000.3(VCL):c.1932C>T(p.Ala644=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
VCL
NM_014000.3 synonymous
NM_014000.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.648
Genes affected
VCL (HGNC:12665): (vinculin) Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane. Defects in VCL are the cause of cardiomyopathy dilated type 1W. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
?
Variant 10-74101007-C-T is Benign according to our data. Variant chr10-74101007-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 536719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.648 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.1932C>T | p.Ala644= | synonymous_variant | 14/22 | ENST00000211998.10 | |
VCL | NM_003373.4 | c.1932C>T | p.Ala644= | synonymous_variant | 14/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.1932C>T | p.Ala644= | synonymous_variant | 14/22 | 1 | NM_014000.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152004Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
2
AN:
152004
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: 0.0000796 AC: 20AN: 251252Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135808
GnomAD3 exomes
AF:
AC:
20
AN:
251252
Hom.:
AF XY:
AC XY:
10
AN XY:
135808
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: 0.0000144 AC: 21AN: 1461764Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727186
GnomAD4 exome
AF:
AC:
21
AN:
1461764
Hom.:
Cov.:
31
AF XY:
AC XY:
10
AN XY:
727186
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: 0.0000132 AC: 2AN: 152004Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74238
GnomAD4 genome
?
AF:
AC:
2
AN:
152004
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74238
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:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dilated cardiomyopathy 1W Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 13, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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