3-8770725-T-C

Variant names:

• chr3-8770725-T-C
• rs2268498
• ENST00000472766.1:n.156-6752T>C

Variant summary

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

The ENST00000472766.1(CAV3):​n.156-6752T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,010 control chromosomes in the GnomAD database, including 13,179 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 0.41 (13179 hom., cov: 32)
• Consequence: CAV3 ENST00000472766.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

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=-0.91).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000472766.1	n.156-6752T>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62706 AN: 151892 Hom.: 13183 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.413 AC: 62727 AN: 152010 Hom.: 13179 Cov.: 32 AF XY: 0.413 AC XY: 30698 AN XY: 74292

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.433

Alfa AF: 0.409 Hom.: 1778

Bravo AF: 0.401

Asia WGS AF: 0.330 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2268498; hg19: chr3-8812411;