10-74043073-C-G

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

Scores

2
Splicing: ADA: 0.00008705
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.674
Variant links:
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
VCLNM_014000.3 linkuse as main transcriptc.169-10C>G splice_polypyrimidine_tract_variant, intron_variant ENST00000211998.10 NP_054706.1
VCLNM_003373.4 linkuse as main transcriptc.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
VCLENST00000211998.10 linkuse as main transcriptc.169-10C>G splice_polypyrimidine_tract_variant, intron_variant 1 NM_014000.3 ENSP00000211998 P18206-1

Frequencies

GnomAD3 genomes
AF:
0.0000990
AC:
15
AN:
151544
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000999
AC:
25
AN:
250240
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135360
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.000491
GnomAD4 exome
AF:
0.0000665
AC:
97
AN:
1457914
Hom.:
0
Cov.:
30
AF XY:
0.0000676
AC XY:
49
AN XY:
725380
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000202
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000757
Gnomad4 OTH exome
AF:
0.0000664
GnomAD4 genome
AF:
0.0000989
AC:
15
AN:
151662
Hom.:
0
Cov.:
32
AF XY:
0.0000540
AC XY:
4
AN XY:
74108
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000260
Hom.:
0
Bravo
AF:
0.0000945

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 18, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
10
DANN
Benign
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000087
dbscSNV1_RF
Benign
0.0040
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs778769534; hg19: chr10-75802831; API