10-73997822-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000623461.3(VCL):n.79+601A>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 0.758 in 152,094 control chromosomes in the GnomAD database, including 44,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.76 (44684 hom., cov: 33)
• Consequence: VCL ENST00000623461.3 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.663

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=-0.23).
• BP6: Variant 10-73997822-A-G is Benign according to our data. Variant chr10-73997822-A-G is described in ClinVar as [Benign]. Clinvar id is 684057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 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
VCL	ENST00000623461.3	n.79+601A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115215 AN: 151974 Hom.: 44641 Cov.: 33

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.758 AC: 115308 AN: 152094 Hom.: 44684 Cov.: 33 AF XY: 0.748 AC XY: 55614 AN XY: 74354

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.773

Alfa AF: 0.774 Hom.: 5700

Bravo AF: 0.766

Asia WGS AF: 0.441 AC: 1535 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

This 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	-0.23
Cadd	Benign	16
Dann	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3812624; hg19: chr10-75757580;