10-74043073-C-G
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_014000.3(VCL):c.169-10C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000696 in 1,609,576 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 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000067 ( 0 hom. )
Consequence
VCL
NM_014000.3 splice_polypyrimidine_tract, intron
NM_014000.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00008705
2
Clinical Significance
Conservation
PhyloP100: 0.674
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.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 10-74043073-C-G is Benign according to our data. Variant chr10-74043073-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 536723.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.169-10C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000211998.10 | NP_054706.1 | |||
VCL | NM_003373.4 | c.169-10C>G | splice_polypyrimidine_tract_variant, intron_variant | NP_003364.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.169-10C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_014000.3 | ENSP00000211998 |
Frequencies
GnomAD3 genomes AF: 0.0000990 AC: 15AN: 151544Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000999 AC: 25AN: 250240Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135360
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GnomAD4 exome AF: 0.0000665 AC: 97AN: 1457914Hom.: 0 Cov.: 30 AF XY: 0.0000676 AC XY: 49AN XY: 725380
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GnomAD4 genome AF: 0.0000989 AC: 15AN: 151662Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4AN XY: 74108
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dilated cardiomyopathy 1W Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at