Genetic Variant CAPN10:c.1482-45C>T (chr2-240596636-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_023083.4(CAPN10):c.1482-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,528,980 control chromosomes in the GnomAD database, including 24,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2319 hom., cov: 34)

Exomes 𝑓: 0.18 ( 22466 hom. )

Consequence

CAPN10
NM_023083.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.608

Publications

15 publications found

Variant links:

Genes affected

CAPN10 (HGNC:1477): (calpain 10) Calpains represent a ubiquitous, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM), and is located within the NIDDM1 region. Multiple alternative transcript variants have been described for this gene. [provided by RefSeq, Sep 2010]

CAPN10 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

CAPN10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN10	NM_023083.4 link	c.1482-45C>T		intron_variant	Intron 8 of 11	ENST00000391984.7	NP_075571.2
CAPN10	NM_023085.4 link	c.1279-1252C>T		intron_variant	Intron 7 of 9		NP_075573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN10	ENST00000391984.7 link	c.1482-45C>T		intron_variant	Intron 8 of 11	1	NM_023083.4	ENSP00000375844.2

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25451

AN:

152134

Hom.:

2323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.0878

Gnomad EAS

AF:

0.290

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.159

GnomAD2 exomes

AF:

0.194

AC:

34865

AN:

179982

AF XY:

0.191

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.0976

Gnomad EAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.177

AC:

243797

AN:

1376728

Hom.:

22466

Cov.:

AF XY:

0.177

AC XY:

119267

AN XY:

675466

show subpopulations

African (AFR)

AF:

0.113

AC:

3484

AN:

30904

American (AMR)

AF:

0.257

AC:

8616

AN:

33484

Ashkenazi Jewish (ASJ)

AF:

0.0956

AC:

1978

AN:

20700

East Asian (EAS)

AF:

0.308

AC:

11962

AN:

38880

South Asian (SAS)

AF:

0.198

AC:

14378

AN:

72588

European-Finnish (FIN)

AF:

0.222

AC:

10577

AN:

47682

Middle Eastern (MID)

AF:

0.149

AC:

737

AN:

4958

European-Non Finnish (NFE)

AF:

0.170

AC:

182376

AN:

1070918

Other (OTH)

AF:

0.171

AC:

9689

AN:

56614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

11441

22881

34322

45762

57203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6782

13564

20346

27128

33910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.167

AC:

25458

AN:

152252

Hom.:

2319

Cov.:

AF XY:

0.172

AC XY:

12817

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.115

AC:

4767

AN:

41550

American (AMR)

AF:

0.225

AC:

3446

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0878

AC:

305

AN:

3472

East Asian (EAS)

AF:

0.290

AC:

1497

AN:

5162

South Asian (SAS)

AF:

0.206

AC:

995

AN:

4830

European-Finnish (FIN)

AF:

0.220

AC:

2335

AN:

10612

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.171

AC:

11607

AN:

68004

Other (OTH)

AF:

0.158

AC:

335

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1129

2259

3388

4518

5647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.164

Hom.:

556

Bravo

AF:

0.165

Asia WGS

AF:

0.246

AC:

857

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.4

(source)

DANN

Benign

0.80

PhyloP100

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over