3-8769967-G-T

Variant names:

• chr3-8769967-G-T
• rs1465386
• ENST00000472766.1:n.156-7510G>T

Variant summary

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

The ENST00000472766.1(CAV3):​n.156-7510G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,126 control chromosomes in the GnomAD database, including 1,250 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 0.11 (1250 hom., cov: 32)
• Consequence: CAV3 ENST00000472766.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.824

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000472766.1	n.156-7510G>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16930 AN: 152008 Hom.: 1251 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0861

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0307

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.111 AC: 16940 AN: 152126 Hom.: 1250 Cov.: 32 AF XY: 0.108 AC XY: 8041 AN XY: 74374

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.0858

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0698

Gnomad4 FIN AF: 0.0307

Gnomad4 NFE AF: 0.0691

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0638 Hom.: 189

Bravo AF: 0.119

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1465386; hg19: chr3-8811653;