rs116840772

Positions:

• chr3-8745478-AAGCGGGTGGCTTCTGTG-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000343849.3(CAV3):​c.115-45_115-29del 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. 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 ENST00000343849.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.481

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:):

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 31736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-8745478-AAGCGGGTGGCTTCTGTG-A is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
CAV3	NM_033337.3	c.115-45_115-29del		intron_variant		ENST00000343849.3	NP_203123.1
CAV3	NM_001234.5	c.115-45_115-29del		intron_variant			NP_001225.1
OXTR	XR_007095681.1	n.1885-2893_1885-2877del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000343849.3	c.115-45_115-29del		intron_variant		1	NM_033337.3	ENSP00000341940	P1
CAV3	ENST00000397368.2	c.115-45_115-29del		intron_variant		1		ENSP00000380525	P1
CAV3	ENST00000472766.1	n.155+11491_155+11507del		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.0933 AC: 22749 AN: 243954 Hom.: 1360 AF XY: 0.0940 AC XY: 12409 AN XY: 131998

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 SAS exome AF: 0.0303

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

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.0626

Gnomad4 ASJ exome AF: 0.0797

Gnomad4 EAS exome AF: 0.00164

Gnomad4 SAS exome AF: 0.0317

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.106

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

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.0849

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.0276

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.101

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 11, 2018	- -
not provided, no classification provided	curation	Leiden Muscular Dystrophy (CAV3)	Apr 15, 2012	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs116840772; hg19: chr3-8787164;