Variant chr15-42386320-G-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 NM_000070.3(CAPN3):c.498+35G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,440,688 control chromosomes in the GnomAD database, including 739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 408 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 331 hom. )

Consequence

CAPN3
NM_000070.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.762

Variant links:

Genes affected

CAPN3 (HGNC:1480): (calpain 3) Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed. [provided by RefSeq, Jul 2008]

CAPN3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-42386320-G-T is Benign according to our data. Variant chr15-42386320-G-T is described in ClinVar as [Benign]. Clinvar id is 254874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-42386320-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CAPN3	NM_000070.3 linkuse as main transcript	c.498+35G>T	intron_variant	ENST00000397163.8
CAPN3	NM_024344.2 linkuse as main transcript	c.498+35G>T	intron_variant
CAPN3	NM_173087.2 linkuse as main transcript	c.498+35G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPN3	ENST00000397163.8 linkuse as main transcript	c.498+35G>T		intron_variant		1	NM_000070.3	P2	P20807-1

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6312

AN:

152074

Hom.:

398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0198

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00306

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0159

AC:

3989

AN:

250662

Hom.:

181

AF XY:

0.0145

AC XY:

1962

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.135

Gnomad AMR exome

AF:

0.00992

Gnomad ASJ exome

AF:

0.0289

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0221

Gnomad FIN exome

AF:

0.0000950

Gnomad NFE exome

AF:

0.00357

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.00798

AC:

10280

AN:

1288496

Hom.:

331

Cov.:

AF XY:

0.00823

AC XY:

5352

AN XY:

650138

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.0270

Gnomad4 EAS exome

AF:

0.0000771

Gnomad4 SAS exome

AF:

0.0225

Gnomad4 FIN exome

AF:

0.000170

Gnomad4 NFE exome

AF:

0.00228

Gnomad4 OTH exome

AF:

0.0155

GnomAD4 genome

AF:

0.0417

AC:

6353

AN:

152192

Hom.:

408

Cov.:

AF XY:

0.0404

AC XY:

3003

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.0199

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0228

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00306

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0162

Hom.:

Bravo

AF:

0.0463

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Muscular dystrophy, limb-girdle, autosomal dominant 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive limb-girdle muscular dystrophy type 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.22

DANN

Benign

0.35

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