rs6777726

chr3-8771808-G-Achr3-8771808-G-T

Variant summary

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

The ENST00000472766.1(CAV3):n.156-5669G>A 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 0.0784 in 150,942 control chromosomes in the GnomAD database, including 473 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 0.078 (473 hom., cov: 33)
• Consequence: CAV3 ENST00000472766.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

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 (EAS) allele frequency at 95% confidence interval = 0.118 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.156-5669G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11826 AN: 150824 Hom.: 474 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0199

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.110

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.0784 AC: 11832 AN: 150942 Hom.: 473 Cov.: 33 AF XY: 0.0765 AC XY: 5641 AN XY: 73720

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0633

Gnomad4 FIN AF: 0.0313

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.0909

Alfa AF: 0.0689 Hom.: 561

Bravo AF: 0.0816

Asia WGS AF: 0.0900 AC: 312 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	2.2
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6777726; hg19: chr3-8813494;