rs237917

Variant names:

• chr3-8771013-T-C
• rs237917
• ENST00000472766.1:n.156-6464T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-8771013-T-C
• chr3-8771013-T-G

Variant summary

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

The ENST00000472766.1(CAV3):​n.156-6464T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,624 control chromosomes in the GnomAD database, including 33,491 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 0.66 (33491 hom., cov: 32)
• Consequence: CAV3 ENST00000472766.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 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.156-6464T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99364 AN: 151506 Hom.: 33481 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.656 AC: 99413 AN: 151624 Hom.: 33491 Cov.: 32 AF XY: 0.649 AC XY: 48106 AN XY: 74086

African (AFR) AF: 0.572 AC: 23625 AN: 41274

American (AMR) AF: 0.577 AC: 8803 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2464 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1622 AN: 5158

South Asian (SAS) AF: 0.722 AC: 3473 AN: 4812

European-Finnish (FIN) AF: 0.652 AC: 6839 AN: 10494

Middle Eastern (MID) AF: 0.779 AC: 226 AN: 290

European-Non Finnish (NFE) AF: 0.740 AC: 50228 AN: 67846

Other (OTH) AF: 0.684 AC: 1443 AN: 2110

Alfa AF: 0.619 Hom.: 9720

Bravo AF: 0.645

Asia WGS AF: 0.480 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.4
DANN	Benign	0.51
PhyloP100		0.12

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: rs237917;

hg19: chr3-8812699;