3-8745503-G-C

Variant names:

• chr3-8745503-G-C
• rs57159780
• NM_033337.3:c.115-23G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2 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: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

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CAV3	NM_033337.3	c.115-23G>C		intron_variant	Intron 1 of 1	ENST00000343849.3	NP_203123.1
CAV3	NM_001234.5	c.115-23G>C		intron_variant	Intron 1 of 2		NP_001225.1
OXTR	XR_007095681.1	n.1885-2901C>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000343849.3	c.115-23G>C		intron_variant	Intron 1 of 1	1	NM_033337.3	ENSP00000341940.2
CAV3	ENST00000397368.2	c.115-23G>C		intron_variant	Intron 1 of 2	1		ENSP00000380525.2
CAV3	ENST00000472766.1	n.155+11513G>C		intron_variant	Intron 1 of 2	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:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1 Other:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 15, 2012

Leiden Muscular Dystrophy (CAV3)

Significance: not provided

Review Status: no classification provided

Collection Method: curation

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;