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10-73997944-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The ENST00000623461.3(VCL):n.79+723A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,044 control chromosomes in the GnomAD database, including 9,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.34 ( 9969 hom., cov: 33)

Consequence

VCL
ENST00000623461.3 intron, non_coding_transcript

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 10-73997944-A-G is Benign according to our data. Variant chr10-73997944-A-G is described in ClinVar as [Benign]. Clinvar id is 684060.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VCLENST00000623461.3 linkuse as main transcriptn.79+723A>G intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.340
AC:
51605
AN:
151926
Hom.:
9931
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.530
Gnomad AMI
AF:
0.164
Gnomad AMR
AF:
0.313
Gnomad ASJ
AF:
0.309
Gnomad EAS
AF:
0.273
Gnomad SAS
AF:
0.280
Gnomad FIN
AF:
0.289
Gnomad MID
AF:
0.304
Gnomad NFE
AF:
0.251
Gnomad OTH
AF:
0.319
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.340
AC:
51699
AN:
152044
Hom.:
9969
Cov.:
33
AF XY:
0.341
AC XY:
25342
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.531
Gnomad4 AMR
AF:
0.314
Gnomad4 ASJ
AF:
0.309
Gnomad4 EAS
AF:
0.273
Gnomad4 SAS
AF:
0.279
Gnomad4 FIN
AF:
0.289
Gnomad4 NFE
AF:
0.251
Gnomad4 OTH
AF:
0.320
Alfa
AF:
0.189
Hom.:
570
Bravo
AF:
0.346
Asia WGS
AF:
0.305
AC:
1062
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
21
Dann
Benign
0.74

Splicing

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: rs3812625; hg19: chr10-75757702; API