rs2131960

Positions:

• chr10-74071501-C-A
• chr10-74071501-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014000.3(VCL):​c.499+418C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,044 control chromosomes in the GnomAD database, including 34,485 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 0.66 (34485 hom., cov: 32)
• Consequence: VCL NM_014000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCL	NM_014000.3	c.499+418C>A		intron_variant		ENST00000211998.10	NP_054706.1
VCL	NM_003373.4	c.499+418C>A		intron_variant			NP_003364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCL	ENST00000211998.10	c.499+418C>A		intron_variant		1	NM_014000.3	ENSP00000211998

Frequencies

GnomAD3 genomes AF: 0.665 AC: 100956 AN: 151926 Hom.: 34457 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.672

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.664 AC: 101031 AN: 152044 Hom.: 34485 Cov.: 32 AF XY: 0.659 AC XY: 48950 AN XY: 74300

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.667

Alfa AF: 0.632 Hom.: 15062

Bravo AF: 0.669

Asia WGS AF: 0.389 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs2131960; hg19: chr10-75831259;