Variant 10-113729393-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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, single submitter B:1

Conservation

PhyloP100: -0.741

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 id is 1246573.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
CASP7	NM_001227.5 linkuse as main transcript	c.765C>G	p.Asp255Glu	missense_variant	7/7	ENST00000369318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP7	ENST00000369318.8 linkuse as main transcript	c.765C>G	p.Asp255Glu	missense_variant	7/7	1	NM_001227.5	P1	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

GnomAD3 exomes

AF:

0.261

AC:

65714

AN:

251392

Hom.:

9012

AF XY:

0.259

AC XY:

35235

AN XY:

135872

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 SAS exome

AF:

0.238

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

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.277

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.446

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.261

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.231

AC:

35122

AN:

152082

Hom.:

4402

Cov.:

AF XY:

0.232

AC XY:

17245

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.421

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.262

Gnomad4 OTH

AF:

0.225

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 23, 2021

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

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

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.28

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over