dbSNP rs41266971: CAPN10:c.471-233A>C (chr2-240591700-A-C) – 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.471-233A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0744 in 567,468 control chromosomes in the GnomAD database, including 1,856 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 0.089 ( 691 hom., cov: 34)

Exomes 𝑓: 0.069 ( 1165 hom. )

Consequence

CAPN10
NM_023083.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.382

Publications

5 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN10	NM_023083.4 link	c.471-233A>C		intron_variant	Intron 3 of 11	ENST00000391984.7	NP_075571.2	Q9HC96-1
CAPN10	NM_023085.4 link	c.471-233A>C		intron_variant	Intron 3 of 9		NP_075573.3	Q9HC96-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN10	ENST00000391984.7 link	c.471-233A>C		intron_variant	Intron 3 of 11	1	NM_023083.4	ENSP00000375844.2		Q9HC96-1

Frequencies

GnomAD3 genomes

AF:

0.0889

AC:

13529

AN:

152176

Hom.:

688

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0472

Gnomad ASJ

AF:

0.0821

Gnomad EAS

AF:

0.0295

Gnomad SAS

AF:

0.0554

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0732

Gnomad OTH

AF:

0.0765

GnomAD4 exome

AF:

0.0691

AC:

28671

AN:

415174

Hom.:

1165

Cov.:

AF XY:

0.0685

AC XY:

14781

AN XY:

215638

show subpopulations

African (AFR)

AF:

0.136

AC:

1623

AN:

11958

American (AMR)

AF:

0.0393

AC:

655

AN:

16654

Ashkenazi Jewish (ASJ)

AF:

0.0815

AC:

1078

AN:

13228

East Asian (EAS)

AF:

0.0194

AC:

577

AN:

29692

South Asian (SAS)

AF:

0.0579

AC:

2163

AN:

37354

European-Finnish (FIN)

AF:

0.0989

AC:

2804

AN:

28362

Middle Eastern (MID)

AF:

0.0786

AC:

149

AN:

1896

European-Non Finnish (NFE)

AF:

0.0710

AC:

17838

AN:

251390

Other (OTH)

AF:

0.0724

AC:

1784

AN:

24640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1252

2504

3756

5008

6260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.0889

AC:

13543

AN:

152294

Hom.:

691

Cov.:

AF XY:

0.0894

AC XY:

6659

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.139

AC:

5764

AN:

41560

American (AMR)

AF:

0.0471

AC:

721

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0821

AC:

285

AN:

3472

East Asian (EAS)

AF:

0.0293

AC:

152

AN:

5182

South Asian (SAS)

AF:

0.0548

AC:

265

AN:

4834

European-Finnish (FIN)

AF:

0.110

AC:

1166

AN:

10604

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0732

AC:

4979

AN:

68024

Other (OTH)

AF:

0.0766

AC:

162

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

662

1323

1985

2646

3308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0354

Hom.:

Bravo

AF:

0.0864

Asia WGS

AF:

0.0430

AC:

151

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.7

(source)

DANN

Benign

0.49

PhyloP100

-0.38

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

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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