rs13010627

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032977.4(CASP10):c.1228G>A(p.Val410Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 1,614,048 control chromosomes in the GnomAD database, including 3,002 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 175 hom., cov: 31)

Exomes 𝑓: 0.058 ( 2827 hom. )

Consequence

CASP10
NM_032977.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.528

Publications

53 publications found

Variant links:

Genes affected

CASP10 (HGNC:1500): (caspase 10) This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene are associated with type IIA autoimmune lymphoproliferative syndrome, non-Hodgkin lymphoma and gastric cancer. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

CASP10 Gene-Disease associations (from GenCC):

autoimmune lymphoproliferative syndrome type 2A
Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
autoimmune lymphoproliferative syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CASP10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017305046).

BP6

Variant 2-201209375-G-A is Benign according to our data. Variant chr2-201209375-G-A is described in ClinVar as Benign. ClinVar VariationId is 21727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CASP10	NM_032977.4	MANE Select	c.1228G>A	p.Val410Ile	missense	Exon 9 of 10	NP_116759.2
CASP10	NM_032974.5		c.1228G>A	p.Val410Ile	missense	Exon 9 of 10	NP_116756.2
CASP10	NM_001230.5		c.1099G>A	p.Val367Ile	missense	Exon 7 of 8	NP_001221.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CASP10	ENST00000286186.11	TSL:1 MANE Select	c.1228G>A	p.Val410Ile	missense	Exon 9 of 10	ENSP00000286186.6	Q92851-4
CASP10	ENST00000448480.1	TSL:1	c.1099G>A	p.Val367Ile	missense	Exon 7 of 8	ENSP00000396835.1	Q92851-5
CASP10	ENST00000313728.12	TSL:1	c.1027G>A	p.Val343Ile	missense	Exon 7 of 8	ENSP00000314599.7	Q92851-6

Frequencies

GnomAD3 genomes

AF:

0.0420

AC:

6382

AN:

152054

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.0573

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0649

Gnomad OTH

AF:

0.0464

GnomAD2 exomes

AF:

0.0419

AC:

10531

AN:

251078

AF XY:

0.0425

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.0274

Gnomad ASJ exome

AF:

0.0413

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0509

Gnomad NFE exome

AF:

0.0642

Gnomad OTH exome

AF:

0.0470

GnomAD4 exome

AF:

0.0583

AC:

85185

AN:

1461876

Hom.:

2827

Cov.:

AF XY:

0.0569

AC XY:

41407

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00917

AC:

307

AN:

33480

American (AMR)

AF:

0.0286

AC:

1277

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0420

AC:

1097

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0102

AC:

876

AN:

86258

European-Finnish (FIN)

AF:

0.0565

AC:

3019

AN:

53418

Middle Eastern (MID)

AF:

0.0189

AC:

109

AN:

5768

European-Non Finnish (NFE)

AF:

0.0678

AC:

75398

AN:

1111998

Other (OTH)

AF:

0.0513

AC:

3097

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4760

9520

14279

19039

23799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2760

5520

8280

11040

13800

<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:

0.0419

AC:

6381

AN:

152172

Hom.:

175

Cov.:

AF XY:

0.0389

AC XY:

2897

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0122

AC:

508

AN:

41512

American (AMR)

AF:

0.0360

AC:

550

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

136

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.00622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0573

AC:

607

AN:

10596

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0648

AC:

4410

AN:

68014

Other (OTH)

AF:

0.0459

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

296

592

889

1185

1481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0559

Hom.:

746

Bravo

AF:

0.0400

TwinsUK

AF:

0.0690

AC:

256

ALSPAC

AF:

0.0729

AC:

281

ESP6500AA

AF:

0.0159

AC:

ESP6500EA

AF:

0.0659

AC:

567

ExAC

AF:

0.0425

AC:

5165

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0623

EpiControl

AF:

0.0640

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Autoimmune lymphoproliferative syndrome type 2A (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.041

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.68

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

0.53

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.71

REVEL

Benign

0.12

Sift

Benign

0.11

Sift4G

Benign

0.19

Polyphen

0.99

Vest4

0.026

MPC

0.15

ClinPred

0.0077

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.080

gMVP

0.25

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over