16-547059-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005632.3(CAPN15):c.221C>T(p.Ala74Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,603,302 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0049 ( 23 hom. )

Consequence

CAPN15
NM_005632.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.494

Publications

5 publications found

Variant links:

Genes affected

CAPN15 (HGNC:11182): (calpain 15) This gene encodes a protein containing zinc-finger-like repeats and a calpain-like protease domain. The encoded protein may function as a transcription factor, RNA-binding protein, or in protein-protein interactions during visual system development. [provided by RefSeq, Jul 2008]

CAPN15 Gene-Disease associations (from GenCC):

oculogastrointestinal-neurodevelopmental syndrome
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

CAPN15 links:

ENSG00000261691 (HGNC:):

ENSG00000261691 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036720634).

BP6

Variant 16-547059-C-T is Benign according to our data. Variant chr16-547059-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645791.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00376 (573/152390) while in subpopulation NFE AF = 0.00588 (400/68044). AF 95% confidence interval is 0.0054. There are 2 homozygotes in GnomAd4. There are 263 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN15	NM_005632.3 link	c.221C>T	p.Ala74Val	missense_variant	Exon 4 of 14	ENST00000219611.7	NP_005623.1	O75808-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN15	ENST00000219611.7 link	c.221C>T	p.Ala74Val	missense_variant	Exon 4 of 14	1	NM_005632.3	ENSP00000219611.2		O75808-1

Frequencies

GnomAD3 genomes

AF:

0.00376

AC:

573

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.00527

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00588

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00360

AC:

826

AN:

229248

AF XY:

0.00349

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.000836

Gnomad ASJ exome

AF:

0.00425

Gnomad EAS exome

AF:

0.0000577

Gnomad FIN exome

AF:

0.00649

Gnomad NFE exome

AF:

0.00529

Gnomad OTH exome

AF:

0.00444

GnomAD4 exome

AF:

0.00488

AC:

7085

AN:

1450912

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

3403

AN XY:

721544

show subpopulations

African (AFR)

AF:

0.000630

AC:

AN:

33356

American (AMR)

AF:

0.000838

AC:

AN:

44154

Ashkenazi Jewish (ASJ)

AF:

0.00457

AC:

118

AN:

25810

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39398

South Asian (SAS)

AF:

0.00222

AC:

190

AN:

85418

European-Finnish (FIN)

AF:

0.00709

AC:

341

AN:

48122

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00555

AC:

6151

AN:

1108942

Other (OTH)

AF:

0.00374

AC:

224

AN:

59970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

442

884

1325

1767

2209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00376

AC:

573

AN:

152390

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

263

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41594

American (AMR)

AF:

0.00229

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00290

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00527

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00588

AC:

400

AN:

68044

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

107

134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00484

Hom.:

Bravo

AF:

0.00320

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00208

AC:

ESP6500EA

AF:

0.00503

AC:

ExAC

AF:

0.00357

AC:

428

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CAPN15: BP4, BS2 -

CAPN15-related disorder

Benign:1

Oct 14, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

0.34

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.010

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.26

.;N;.

PhyloP100

-0.49

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

N;N;.

REVEL

Benign

0.20

Sift

Benign

0.37

T;T;.

Sift4G

Benign

0.36

T;T;.

Polyphen

0.0010

.;B;.

Vest4

0.039

MVP

0.69

ClinPred

0.000095

GERP RS

-4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.015

gMVP

0.21

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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16-547059-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over