Variant 3-8745481-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000343849.3(CAV3):c.115-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 1,147,046 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 105 hom., cov: 30)

Exomes 𝑓: 0.0029 ( 94 hom. )

Consequence

CAV3
ENST00000343849.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.50

Variant links:

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]

CAV3 links:

OXTR (HGNC:):

OXTR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 3-8745481-C-T is Benign according to our data. Variant chr3-8745481-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CAV3	NM_033337.3 linkuse as main transcript	c.115-45C>T	intron_variant	ENST00000343849.3	NP_203123.1
CAV3	NM_001234.5 linkuse as main transcript	c.115-45C>T	intron_variant		NP_001225.1
OXTR	XR_007095681.1 linkuse as main transcript	n.1885-2879G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
CAV3	ENST00000343849.3 linkuse as main transcript	c.115-45C>T	intron_variant	1	NM_033337.3	ENSP00000341940	P1
CAV3	ENST00000397368.2 linkuse as main transcript	c.115-45C>T	intron_variant	1		ENSP00000380525	P1
CAV3	ENST00000472766.1 linkuse as main transcript	n.155+11491C>T	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

2989

AN:

126764

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00764

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000438

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0179

Gnomad NFE

AF:

0.000296

Gnomad OTH

AF:

0.0136

GnomAD3 exomes

AF:

0.00538

AC:

1313

AN:

244164

Hom.:

AF XY:

0.00381

AC XY:

503

AN XY:

132032

show subpopulations

Gnomad AFR exome

AF:

0.0731

Gnomad AMR exome

AF:

0.00302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000551

Gnomad SAS exome

AF:

0.000303

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000219

Gnomad OTH exome

AF:

0.00233

GnomAD4 exome

AF:

0.00294

AC:

2997

AN:

1020162

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

1320

AN XY:

516238

show subpopulations

Gnomad4 AFR exome

AF:

0.0784

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.000271

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000264

Gnomad4 OTH exome

AF:

0.00695

GnomAD4 genome

AF:

0.0237

AC:

3006

AN:

126884

Hom.:

105

Cov.:

AF XY:

0.0225

AC XY:

1406

AN XY:

62372

show subpopulations

Gnomad4 AFR

AF:

0.0720

Gnomad4 AMR

AF:

0.00763

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000438

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000296

Gnomad4 OTH

AF:

0.0164

Alfa

AF:

0.0281

Hom.:

Bravo

AF:

0.0225

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.024

DANN

Benign

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over