3-8770725-T-C

Variant names:

• chr3-8770725-T-C
• rs2268498
• ENST00000472766.1:n.156-6752T>C

Variant summary

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

The ENST00000472766.1(CAV3):​n.156-6752T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,010 control chromosomes in the GnomAD database, including 13,179 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 0.41 (13179 hom., cov: 32)
• Consequence: CAV3 ENST00000472766.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 69 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
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000472766.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV3	ENST00000472766.1	TSL:2	n.156-6752T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62706 AN: 151892 Hom.: 13183 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.413 AC: 62727 AN: 152010 Hom.: 13179 Cov.: 32 AF XY: 0.413 AC XY: 30698 AN XY: 74292

African (AFR) AF: 0.342 AC: 14158 AN: 41454

American (AMR) AF: 0.381 AC: 5826 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1552 AN: 3470

East Asian (EAS) AF: 0.278 AC: 1438 AN: 5168

South Asian (SAS) AF: 0.455 AC: 2196 AN: 4824

European-Finnish (FIN) AF: 0.478 AC: 5048 AN: 10552

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31041 AN: 67946

Other (OTH) AF: 0.433 AC: 916 AN: 2116

Alfa AF: 0.409 Hom.: 1778

Bravo AF: 0.401

Asia WGS AF: 0.330 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.60
PhyloP100		-0.47

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2268498;

hg19: chr3-8812411;