rs116840772

Variant names:

• chr3-8745478-AAGCGGGTGGCTTCTGTG-A
• rs116840772
• NM_033337.3:c.115-45_115-29delCGGGTGGCTTCTGTGAG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_033337.3(CAV3):​c.115-45_115-29delCGGGTGGCTTCTGTGAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,486,724 control chromosomes in the GnomAD database, including 12,384 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (793 hom., cov: 30)
  • Exomes 𝑓: 0.13 (11591 hom.)
• Consequence: CAV3 NM_033337.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.481
• Publications: 2 publications found

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]

OXTR (HGNC:8529): (oxytocin receptor) The protein encoded by this gene belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Its activity is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. The oxytocin-oxytocin receptor system plays an important role in the uterus during parturition. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 3-8745478-AAGCGGGTGGCTTCTGTG-A is Benign according to our data. Variant chr3-8745478-AAGCGGGTGGCTTCTGTG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 31736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV3	NM_033337.3	c.115-45_115-29delCGGGTGGCTTCTGTGAG		intron_variant	Intron 1 of 1	ENST00000343849.3	NP_203123.1
CAV3	NM_001234.5	c.115-45_115-29delCGGGTGGCTTCTGTGAG		intron_variant	Intron 1 of 2		NP_001225.1
OXTR	XR_007095681.1	n.1885-2893_1885-2877delCACAGAAGCCACCCGCT		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000343849.3	c.115-47_115-31delAGCGGGTGGCTTCTGTG		intron_variant	Intron 1 of 1	1	NM_033337.3	ENSP00000341940.2
CAV3	ENST00000397368.2	c.115-47_115-31delAGCGGGTGGCTTCTGTG		intron_variant	Intron 1 of 2	1		ENSP00000380525.2
CAV3	ENST00000472766.1	n.155+11489_155+11505delAGCGGGTGGCTTCTGTG		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0890 AC: 13534 AN: 152082 Hom.: 792 Cov.: 30

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.0272

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.0933 AC: 22749 AN: 243954 AF XY: 0.0940

Gnomad AFR exome AF: 0.0228

Gnomad AMR exome AF: 0.0601

Gnomad ASJ exome AF: 0.0776

Gnomad EAS exome AF: 0.00204

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.127 AC: 170138 AN: 1334524 Hom.: 11591 AF XY: 0.124 AC XY: 83327 AN XY: 670322

African (AFR) AF: 0.0225 AC: 679 AN: 30130

American (AMR) AF: 0.0626 AC: 2776 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.0797 AC: 2013 AN: 25242

East Asian (EAS) AF: 0.00164 AC: 64 AN: 39062

South Asian (SAS) AF: 0.0317 AC: 2616 AN: 82516

European-Finnish (FIN) AF: 0.129 AC: 6854 AN: 53046

Middle Eastern (MID) AF: 0.0689 AC: 374 AN: 5426

European-Non Finnish (NFE) AF: 0.149 AC: 148793 AN: 998738

Other (OTH) AF: 0.106 AC: 5969 AN: 56054

GnomAD4 genome AF: 0.0889 AC: 13534 AN: 152200 Hom.: 793 Cov.: 30 AF XY: 0.0862 AC XY: 6414 AN XY: 74406

African (AFR) AF: 0.0241 AC: 1003 AN: 41552

American (AMR) AF: 0.0849 AC: 1299 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5184

South Asian (SAS) AF: 0.0276 AC: 133 AN: 4816

European-Finnish (FIN) AF: 0.126 AC: 1334 AN: 10584

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9225 AN: 67986

Other (OTH) AF: 0.101 AC: 214 AN: 2110

Alfa AF: 0.103 Hom.: 141

Bravo AF: 0.0843

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1 Other:1

Apr 15, 2012

Leiden Muscular Dystrophy (CAV3)

Significance: not provided

Review Status: no classification provided

Collection Method: curation

- -

Jul 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs116840772; hg19: chr3-8787164;