rs3806675

Variant names:

• chr3-8769960-G-A
• rs3806675
• ENST00000472766.1:n.156-7517G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000472766.1(CAV3):​n.156-7517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,082 control chromosomes in the GnomAD database, including 8,352 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 0.30 (8352 hom., cov: 33)
• Consequence: CAV3 ENST00000472766.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.705
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• caveolinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant limb-girdle muscular dystrophy type 1C

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• long QT syndrome 9

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• rippling muscle disease 2

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• distal myopathy, Tateyama type

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• inherited rippling muscle disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Brugada syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
• hypertrophic cardiomyopathy 1

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• long QT syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000472766.1	n.156-7517G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45825 AN: 151964 Hom.: 8354 Cov.: 33

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.301 AC: 45822 AN: 152082 Hom.: 8352 Cov.: 33 AF XY: 0.307 AC XY: 22800 AN XY: 74314

African (AFR) AF: 0.0922 AC: 3825 AN: 41508

American (AMR) AF: 0.287 AC: 4391 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1336 AN: 5168

South Asian (SAS) AF: 0.340 AC: 1641 AN: 4830

European-Finnish (FIN) AF: 0.484 AC: 5103 AN: 10540

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27053 AN: 67968

Other (OTH) AF: 0.337 AC: 711 AN: 2110

Alfa AF: 0.327 Hom.: 7647

Bravo AF: 0.276

Asia WGS AF: 0.262 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		0.70
PromoterAI		-0.015	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3806675; hg19: chr3-8811646;