rs762497815
Positions:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_014000.3(VCL):āc.424T>Cā(p.Leu142=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,088 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 (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.0000075 ( 0 hom. )
Consequence
VCL
NM_014000.3 synonymous
NM_014000.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.58
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 -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 10-74071008-T-C is Benign according to our data. Variant chr10-74071008-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 240881.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-74071008-T-C is described in Lovd as [Benign]. Variant chr10-74071008-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.58 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.424T>C | p.Leu142= | synonymous_variant | 4/22 | ENST00000211998.10 | |
VCL | NM_003373.4 | c.424T>C | p.Leu142= | synonymous_variant | 4/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.424T>C | p.Leu142= | synonymous_variant | 4/22 | 1 | NM_014000.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152248Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
2
AN:
152248
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: 0.0000119 AC: 3AN: 251312Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135812
GnomAD3 exomes
AF:
AC:
3
AN:
251312
Hom.:
AF XY:
AC XY:
0
AN XY:
135812
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: 0.00000752 AC: 11AN: 1461840Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727218
GnomAD4 exome
AF:
AC:
11
AN:
1461840
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
727218
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: 0.0000131 AC: 2AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74384
GnomAD4 genome
?
AF:
AC:
2
AN:
152248
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74384
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Dilated cardiomyopathy 1W Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 05, 2022 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
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