15-42409490-T-C

Position:

chr15-42409490-T-C

Variant summary

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

The NM_000070.3(CAPN3):c.1992+110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,109,212 control chromosomes in the GnomAD database, including 284,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 45566 hom., cov: 32)

Exomes 𝑓: 0.70 ( 238714 hom. )

Consequence

CAPN3
NM_000070.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.44

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:

ENSG00000258461 (HGNC:):

ENSG00000258461 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=-0.87).

BP6

Variant 15-42409490-T-C is Benign according to our data. Variant chr15-42409490-T-C is described in ClinVar as [Benign]. Clinvar id is 678278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-42409490-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN3	NM_000070.3 linkuse as main transcript	c.1992+110T>C		intron_variant		ENST00000397163.8	NP_000061.1	P20807-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CAPN3	ENST00000397163.8 linkuse as main transcript	c.1992+110T>C	intron_variant	1	NM_000070.3	ENSP00000380349.3	P20807-1
CAPN3	ENST00000673886.1 linkuse as main transcript	c.-4+110T>C	intron_variant			ENSP00000501155.1	P20807-5
CAPN3	ENST00000673928.1 linkuse as main transcript	c.-4+110T>C	intron_variant			ENSP00000501099.1	P20807-5
CAPN3	ENST00000674146.1 linkuse as main transcript	c.-4+110T>C	intron_variant			ENSP00000501175.1	P20807-5
CAPN3	ENST00000674149.1 linkuse as main transcript	c.-4+110T>C	intron_variant			ENSP00000501112.1	P20807-5
CAPN3	ENST00000673743.1 linkuse as main transcript	c.-101+110T>C	intron_variant			ENSP00000500989.1	A0A669KAX6
ENSG00000258461	ENST00000495723.1 linkuse as main transcript	n.*2428+110T>C	intron_variant	2		ENSP00000492063.1	A0A1W2PQD3

Frequencies

GnomAD3 genomes

AF:

0.764

AC:

116154

AN:

152050

Hom.:

45516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.933

Gnomad AMI

AF:

0.779

Gnomad AMR

AF:

0.733

Gnomad ASJ

AF:

0.791

Gnomad EAS

AF:

0.434

Gnomad SAS

AF:

0.707

Gnomad FIN

AF:

0.673

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.772

GnomAD4 exome

AF:

0.703

AC:

672391

AN:

957044

Hom.:

238714

AF XY:

0.704

AC XY:

345964

AN XY:

491408

show subpopulations

Gnomad4 AFR exome

AF:

0.938

Gnomad4 AMR exome

AF:

0.698

Gnomad4 ASJ exome

AF:

0.782

Gnomad4 EAS exome

AF:

0.439

Gnomad4 SAS exome

AF:

0.728

Gnomad4 FIN exome

AF:

0.660

Gnomad4 NFE exome

AF:

0.705

Gnomad4 OTH exome

AF:

0.719

GnomAD4 genome

AF:

0.764

AC:

116263

AN:

152168

Hom.:

45566

Cov.:

AF XY:

0.759

AC XY:

56431

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.933

Gnomad4 AMR

AF:

0.732

Gnomad4 ASJ

AF:

0.791

Gnomad4 EAS

AF:

0.436

Gnomad4 SAS

AF:

0.708

Gnomad4 FIN

AF:

0.673

Gnomad4 NFE

AF:

0.709

Gnomad4 OTH

AF:

0.767

Alfa

AF:

0.725

Hom.:

56507

Bravo

AF:

0.776

Asia WGS

AF:

0.586

AC:

2038

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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. -

Muscular dystrophy, limb-girdle, autosomal dominant 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Autosomal recessive limb-girdle muscular dystrophy type 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.092

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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