rs6777726

Variant names:

• chr3-8771808-G-A
• rs6777726
• ENST00000472766.1:n.156-5669G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-8771808-G-A
• chr3-8771808-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 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
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000472766.1	n.156-5669G>A		intron_variant	Intron 1 of 2	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;