rs57159780

chr3-8745503-G-C

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.115-23G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 1,594,502 control chromosomes in the GnomAD database, including 5,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (750 hom., cov: 32)
  • Exomes 𝑓: 0.079 (4953 hom.)
• Consequence: CAV3 NM_033337.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 1.08

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-8745503-G-C is Benign according to our data. Variant chr3-8745503-G-C is described in ClinVar as [Benign]. Clinvar id is 31737.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-8745503-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV3	NM_033337.3	c.115-23G>C		intron_variant		ENST00000343849.3
CAV3	NM_001234.5	c.115-23G>C		intron_variant
OXTR	XR_007095681.1	n.1885-2901C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV3	ENST00000343849.3	c.115-23G>C		intron_variant		1	NM_033337.3	P1
CAV3	ENST00000397368.2	c.115-23G>C		intron_variant		1		P1
CAV3	ENST00000472766.1	n.155+11513G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13886 AN: 152018 Hom.: 745 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.00810

Gnomad SAS AF: 0.0324

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0858

Gnomad OTH AF: 0.0627

GnomAD3 exomes AF: 0.0695 AC: 17134 AN: 246556 Hom.: 744 AF XY: 0.0683 AC XY: 9097 AN XY: 133284

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.0287

Gnomad ASJ exome AF: 0.0751

Gnomad EAS exome AF: 0.00441

Gnomad SAS exome AF: 0.0368

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.0827

Gnomad OTH exome AF: 0.0607

GnomAD4 exome AF: 0.0791 AC: 114090 AN: 1442366 Hom.: 4953 Cov.: 29 AF XY: 0.0775 AC XY: 55731 AN XY: 718650

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.0308

Gnomad4 ASJ exome AF: 0.0772

Gnomad4 EAS exome AF: 0.00197

Gnomad4 SAS exome AF: 0.0374

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.0839

Gnomad4 OTH exome AF: 0.0789

GnomAD4 genome AF: 0.0914 AC: 13910 AN: 152136 Hom.: 750 Cov.: 32 AF XY: 0.0920 AC XY: 6843 AN XY: 74370

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0740

Gnomad4 EAS AF: 0.00811

Gnomad4 SAS AF: 0.0326

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0858

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0898 Hom.: 119

Bravo AF: 0.0866

Asia WGS AF: 0.0420 AC: 144 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Other:1

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	-0.81
Cadd	Benign	5.4
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs57159780; hg19: chr3-8787189;