rs56314318

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014000.3(VCL):c.339G>A(p.Arg113Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,974 control chromosomes in the GnomAD database, including 1,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 1035 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 803 hom. )

Consequence

VCL
NM_014000.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.930

Publications

6 publications found

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]

VCL Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: STRONG Submitted by: ClinGen
dilated cardiomyopathy 1W
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypertrophic cardiomyopathy 15
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

VCL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 10-74070769-G-A is Benign according to our data. Variant chr10-74070769-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 36897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014000.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCL	NM_014000.3	MANE Select	c.339G>A	p.Arg113Arg	synonymous	Exon 3 of 22	NP_054706.1	P18206-1
	VCL	NM_003373.4		c.339G>A	p.Arg113Arg	synonymous	Exon 3 of 21	NP_003364.1	P18206-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VCL	ENST00000211998.10	TSL:1 MANE Select	c.339G>A	p.Arg113Arg	synonymous	Exon 3 of 22	ENSP00000211998.5	P18206-1
VCL	ENST00000372755.7	TSL:1	c.339G>A	p.Arg113Arg	synonymous	Exon 3 of 21	ENSP00000361841.3	P18206-2
VCL	ENST00000623461.3	TSL:1	n.297G>A		non_coding_transcript_exon	Exon 5 of 23

Frequencies

GnomAD3 genomes

AF:

0.0626

AC:

9510

AN:

152010

Hom.:

1035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0218

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000971

Gnomad OTH

AF:

0.0407

GnomAD2 exomes

AF:

0.0169

AC:

4244

AN:

251246

AF XY:

0.0127

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.00995

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000845

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00651

AC:

9521

AN:

1461846

Hom.:

803

Cov.:

AF XY:

0.00575

AC XY:

4181

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.215

AC:

7199

AN:

33476

American (AMR)

AF:

0.0108

AC:

481

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

408

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.000672

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0134

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000388

AC:

431

AN:

1111998

Other (OTH)

AF:

0.0144

AC:

867

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

575

1151

1726

2302

2877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

228

456

684

912

1140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0626

AC:

9522

AN:

152128

Hom.:

1035

Cov.:

AF XY:

0.0599

AC XY:

4452

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.216

AC:

8947

AN:

41452

American (AMR)

AF:

0.0218

AC:

333

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00166

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000971

AC:

AN:

67994

Other (OTH)

AF:

0.0403

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

371

741

1112

1482

1853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0302

Hom.:

221

Bravo

AF:

0.0704

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.00113

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Dilated cardiomyopathy 1W (2)

not provided (2)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

Dilated cardiomyopathy 1W;C2750459:Hypertrophic cardiomyopathy 15 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.4

(source)

DANN

Benign

0.57

PhyloP100

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over