rs11922879

chr3-8734016-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033337.3(CAV3):c.114+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 1,382,150 control chromosomes in the GnomAD database, including 2,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (665 hom., cov: 30)
  • Exomes 𝑓: 0.051 (1975 hom.)
• Consequence: CAV3 NM_033337.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.842

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]

SSUH2 (HGNC:24809): (ssu-2 homolog) Involved in odontogenesis. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-8734016-G-A is Benign according to our data. Variant chr3-8734016-G-A is described in ClinVar as [Benign]. Clinvar id is 31723.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-8734016-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV3	NM_033337.3	c.114+26G>A		intron_variant		ENST00000343849.3
CAV3	NM_001234.5	c.114+26G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV3	ENST00000343849.3	c.114+26G>A		intron_variant		1	NM_033337.3	P1

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11861 AN: 151850 Hom.: 663 Cov.: 30

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.00464

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0680

GnomAD3 exomes AF: 0.0498 AC: 12196 AN: 244726 Hom.: 456 AF XY: 0.0481 AC XY: 6375 AN XY: 132458

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.0226

Gnomad ASJ exome AF: 0.0465

Gnomad EAS exome AF: 0.00293

Gnomad SAS exome AF: 0.0406

Gnomad FIN exome AF: 0.0719

Gnomad NFE exome AF: 0.0501

Gnomad OTH exome AF: 0.0436

GnomAD4 exome AF: 0.0509 AC: 62608 AN: 1230184 Hom.: 1975 Cov.: 17 AF XY: 0.0502 AC XY: 31274 AN XY: 623340

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.0253

Gnomad4 ASJ exome AF: 0.0477

Gnomad4 EAS exome AF: 0.00124

Gnomad4 SAS exome AF: 0.0399

Gnomad4 FIN exome AF: 0.0726

Gnomad4 NFE exome AF: 0.0503

Gnomad4 OTH exome AF: 0.0586

GnomAD4 genome AF: 0.0781 AC: 11874 AN: 151966 Hom.: 665 Cov.: 30 AF XY: 0.0774 AC XY: 5747 AN XY: 74284

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0448

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.00465

Gnomad4 SAS AF: 0.0422

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.0503

Gnomad4 OTH AF: 0.0673

Alfa AF: 0.0612 Hom.: 88

Bravo AF: 0.0770

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1 Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
not provided, no classification provided	curation	Leiden Muscular Dystrophy (CAV3)	Apr 15, 2012	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.31
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11922879; hg19: chr3-8775702;