rs756064535
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_014000.3(VCL):c.874+9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,474 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: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
VCL
NM_014000.3 intron
NM_014000.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0610
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 10-74082553-C-G is Benign according to our data. Variant chr10-74082553-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 228231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.874+9C>G | intron_variant | ENST00000211998.10 | |||
VCL | NM_003373.4 | c.874+9C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.874+9C>G | intron_variant | 1 | NM_014000.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251144Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135736
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461474Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727032
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GnomAD4 genome Cov.: 32
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32
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 10, 2015 | c.874+9C>G in intron 7 of VCL: This variant is not expected to have clinical sig nificance because it is not located within the splice consensus sequence. It has been identified in 1/16342 South Asian chromosomes by the Exome Aggregation Con sortium (ExAC, http://exac.broadinstitute.org; dbSNP rs756064535). - |
Dilated cardiomyopathy 1W Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 08, 2020 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at