rs2227310

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001227.5(CASP7):c.765C>G(p.Asp255Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,613,424 control chromosomes in the GnomAD database, including 55,528 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4402 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51126 hom. )

Consequence

CASP7
NM_001227.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.741

Publications

83 publications found

Variant links:

Genes affected

CASP7 (HGNC:1508): (caspase 7) This gene encodes 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. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

CASP7 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=0.0011807978).

BP6

Variant 10-113729393-C-G is Benign according to our data. Variant chr10-113729393-C-G is described in ClinVar as Benign. ClinVar VariationId is 1246573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5 link	c.765C>G	p.Asp255Glu	missense_variant	Exon 7 of 7	ENST00000369318.8	NP_001218.1	P55210-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8 link	c.765C>G	p.Asp255Glu	missense_variant	Exon 7 of 7	1	NM_001227.5	ENSP00000358324.4		P55210-1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35110

AN:

151964

Hom.:

4399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.224

GnomAD2 exomes

AF:

0.261

AC:

65714

AN:

251392

AF XY:

0.259

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.258

Gnomad OTH exome

AF:

0.258

GnomAD4 exome

AF:

0.261

AC:

381044

AN:

1461342

Hom.:

51126

Cov.:

AF XY:

0.260

AC XY:

188777

AN XY:

727012

show subpopulations

African (AFR)

AF:

0.139

AC:

4651

AN:

33472

American (AMR)

AF:

0.277

AC:

12367

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

5109

AN:

26132

East Asian (EAS)

AF:

0.446

AC:

17698

AN:

39696

South Asian (SAS)

AF:

0.236

AC:

20334

AN:

86248

European-Finnish (FIN)

AF:

0.274

AC:

14625

AN:

53406

Middle Eastern (MID)

AF:

0.232

AC:

1338

AN:

5760

European-Non Finnish (NFE)

AF:

0.261

AC:

290006

AN:

1111524

Other (OTH)

AF:

0.247

AC:

14916

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

15954

31908

47861

63815

79769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9844

19688

29532

39376

49220

<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:

0.231

AC:

35122

AN:

152082

Hom.:

4402

Cov.:

AF XY:

0.232

AC XY:

17245

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.143

AC:

5918

AN:

41508

American (AMR)

AF:

0.238

AC:

3635

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

639

AN:

3472

East Asian (EAS)

AF:

0.421

AC:

2172

AN:

5164

South Asian (SAS)

AF:

0.238

AC:

1148

AN:

4818

European-Finnish (FIN)

AF:

0.272

AC:

2874

AN:

10572

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17828

AN:

67958

Other (OTH)

AF:

0.225

AC:

475

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1411

2822

4233

5644

7055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.242

Hom.:

3645

Bravo

AF:

0.226

TwinsUK

AF:

0.242

AC:

896

ALSPAC

AF:

0.267

AC:

1029

ESP6500AA

AF:

0.145

AC:

638

ESP6500EA

AF:

0.253

AC:

2172

ExAC

AF:

0.260

AC:

31543

Asia WGS

AF:

0.279

AC:

969

AN:

3478

EpiCase

AF:

0.251

EpiControl

AF:

0.246

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 23, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23765963, 19826114) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.5

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.019

T;T;T;T;T;.;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.73

T;.;T;.;.;T;T

MetaRNN

Benign

0.0012

T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

PhyloP100

-0.74

PrimateAI

Benign

0.28

PROVEAN

Benign

0.96

.;N;.;N;N;.;N

REVEL

Benign

0.15

Sift

Benign

0.84

.;T;.;T;T;.;T

Sift4G

Benign

1.0

T;T;T;T;T;T;T

Polyphen

0.0

B;B;.;B;B;B;.

Vest4

0.0060

MutPred

0.11

Gain of disorder (P = 0.0902);Gain of disorder (P = 0.0902);.;Gain of disorder (P = 0.0902);Gain of disorder (P = 0.0902);.;.;

MPC

0.14

ClinPred

0.0019

GERP RS

1.7

Varity_R

0.12

gMVP

0.28

Mutation Taster

=99/1

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over