rs1488467

chr3-8771545-G-C

Variant summary

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

The ENST00000472766.1(CAV3):n.156-5932G>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 0.0638 in 152,172 control chromosomes in the GnomAD database, including 323 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 0.064 (323 hom., cov: 33)
• Consequence: CAV3 ENST00000472766.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 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.156-5932G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9702 AN: 152054 Hom.: 324 Cov.: 33

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0571

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.0742

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

GnomAD4 genome AF: 0.0638 AC: 9706 AN: 152172 Hom.: 323 Cov.: 33 AF XY: 0.0621 AC XY: 4621 AN XY: 74386

Gnomad4 AFR AF: 0.0606

Gnomad4 AMR AF: 0.0608

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0576

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.0659

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.0652 Hom.: 36

Bravo AF: 0.0657

Asia WGS AF: 0.0850 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.4
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1488467; hg19: chr3-8813231;