rs2268497

Positions:

• chr3-8770542-A-G

Variant summary

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

The ENST00000472766.1(CAV3):​n.156-6935A>G 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 0.444 in 152,090 control chromosomes in the GnomAD database, including 15,074 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 0.44 (15074 hom., cov: 33)
• Consequence: CAV3 ENST00000472766.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393

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 = 0.453 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.156-6935A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67525 AN: 151972 Hom.: 15075 Cov.: 33

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.444 AC: 67553 AN: 152090 Hom.: 15074 Cov.: 33 AF XY: 0.444 AC XY: 32986 AN XY: 74352

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.454

Alfa AF: 0.452 Hom.: 3395

Bravo AF: 0.438

Asia WGS AF: 0.336 AC: 1176 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	5.2
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2268497; hg19: chr3-8812228;