rs10762573

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014000.3(VCL):​c.169-4693A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,048 control chromosomes in the GnomAD database, including 34,550 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 34550 hom., cov: 31)

Consequence

VCL
NM_014000.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VCLNM_014000.3 linkuse as main transcriptc.169-4693A>C intron_variant ENST00000211998.10
VCLNM_003373.4 linkuse as main transcriptc.169-4693A>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VCLENST00000211998.10 linkuse as main transcriptc.169-4693A>C intron_variant 1 NM_014000.3 P18206-1

Frequencies

GnomAD3 genomes
AF:
0.666
AC:
101251
AN:
151930
Hom.:
34519
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.760
Gnomad AMI
AF:
0.515
Gnomad AMR
AF:
0.688
Gnomad ASJ
AF:
0.763
Gnomad EAS
AF:
0.298
Gnomad SAS
AF:
0.463
Gnomad FIN
AF:
0.622
Gnomad MID
AF:
0.687
Gnomad NFE
AF:
0.651
Gnomad OTH
AF:
0.678
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.666
AC:
101331
AN:
152048
Hom.:
34550
Cov.:
31
AF XY:
0.661
AC XY:
49144
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.760
Gnomad4 AMR
AF:
0.688
Gnomad4 ASJ
AF:
0.763
Gnomad4 EAS
AF:
0.297
Gnomad4 SAS
AF:
0.463
Gnomad4 FIN
AF:
0.622
Gnomad4 NFE
AF:
0.651
Gnomad4 OTH
AF:
0.675
Alfa
AF:
0.652
Hom.:
41044
Bravo
AF:
0.671
Asia WGS
AF:
0.396
AC:
1380
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.78
DANN
Benign
0.63

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

LitVar

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

Other links and lift over

dbSNP: rs10762573; hg19: chr10-75798148; API