rs401015

Positions:

• chr3-8772326-T-C
• chr3-8772326-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000472766.1(CAV3):​n.156-5151T>C 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 0.198 in 152,150 control chromosomes in the GnomAD database, including 3,594 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 0.20 (3594 hom., cov: 32)
• Consequence: CAV3 ENST00000472766.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 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
CAV3	ENST00000472766.1	n.156-5151T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30070 AN: 152032 Hom.: 3597 Cov.: 32

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0472

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.198 AC: 30072 AN: 152150 Hom.: 3594 Cov.: 32 AF XY: 0.194 AC XY: 14394 AN XY: 74368

Gnomad4 AFR AF: 0.0809

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.0469

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.221

Alfa AF: 0.216 Hom.: 721

Bravo AF: 0.194

Asia WGS AF: 0.148 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs401015; hg19: chr3-8814012;