rs13087941

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033337.3(CAV3):c.123T>C(p.Phe41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,612,768 control chromosomes in the GnomAD database, including 43,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4286 hom., cov: 32)

Exomes 𝑓: 0.22 ( 39429 hom. )

Consequence

CAV3
NM_033337.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14O:1

Conservation

PhyloP100: -0.510

Variant links:

Genes affected

CAV3 (HGNC:1529): (caveolin 3) This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), hyperCKemia or rippling muscle disease (RMD). Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. [provided by RefSeq, Jul 2008]

CAV3 links:

OXTR (HGNC:):

OXTR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-8745534-T-C is Benign according to our data. Variant chr3-8745534-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 31717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-8745534-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CAV3	NM_033337.3 linkuse as main transcript	c.123T>C	p.Phe41=	synonymous_variant	2/2	ENST00000343849.3
CAV3	NM_001234.5 linkuse as main transcript	c.123T>C	p.Phe41=	synonymous_variant	2/3
OXTR	XR_007095681.1 linkuse as main transcript	n.1885-2932A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CAV3	ENST00000343849.3 linkuse as main transcript	c.123T>C	p.Phe41=	synonymous_variant	2/2	1	NM_033337.3	P1
CAV3	ENST00000397368.2 linkuse as main transcript	c.123T>C	p.Phe41=	synonymous_variant	2/3	1		P1
CAV3	ENST00000472766.1 linkuse as main transcript	n.155+11544T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34733

AN:

152002

Hom.:

4283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.0627

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.196

GnomAD3 exomes

AF:

0.182

AC:

45650

AN:

250760

Hom.:

5213

AF XY:

0.178

AC XY:

24175

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.291

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.00658

Gnomad SAS exome

AF:

0.0676

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.222

AC:

323714

AN:

1460648

Hom.:

39429

Cov.:

AF XY:

0.217

AC XY:

157360

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.00348

Gnomad4 SAS exome

AF:

0.0695

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.229

AC:

34765

AN:

152120

Hom.:

4286

Cov.:

AF XY:

0.222

AC XY:

16541

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.286

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.0104

Gnomad4 SAS

AF:

0.0629

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.239

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.226

Hom.:

5459

Bravo

AF:

0.226

Asia WGS

AF:

0.0680

AC:

238

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.221

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:9

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 29, 2017	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2011	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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 29, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 25, 2012	- -

Limb-Girdle Muscular Dystrophy, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Caveolinopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 09, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Other:1

not provided, no classification provided

curation

Leiden Muscular Dystrophy (CAV3)

Apr 15, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

Cadd

Benign

0.21

Dann

Benign

0.49

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over