3-8770725-T-C

Position:

• chr3-8770725-T-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, non coding transcript 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, non_coding_transcript
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV3	ENST00000472766.1	n.156-6752T>C		intron_variant, non_coding_transcript_variant		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;