rs16931177

chr10-74111132-C-Gchr10-74111132-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.2746-777C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,970 control chromosomes in the GnomAD database, including 22,305 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 0.53 (22305 hom., cov: 31)
• Consequence: VCL NM_014000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCL	NM_014000.3	c.2746-777C>G		intron_variant		ENST00000211998.10
VCL	NM_003373.4	c.2745+1976C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCL	ENST00000211998.10	c.2746-777C>G		intron_variant		1	NM_014000.3
VCL	ENST00000372755.7	c.2745+1976C>G		intron_variant		1		P1
VCL	ENST00000623461.3	n.5548+1976C>G		intron_variant, non_coding_transcript_variant		1
VCL	ENST00000624354.3	c.*2501-777C>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80522 AN: 151850 Hom.: 22295 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.626

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.530 AC: 80544 AN: 151970 Hom.: 22305 Cov.: 31 AF XY: 0.527 AC XY: 39153 AN XY: 74266

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.575

Alfa AF: 0.563 Hom.: 2942

Bravo AF: 0.518

Asia WGS AF: 0.327 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.86
Dann	Benign	0.52

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: rs16931177; hg19: chr10-75870890;