Variant rs2227309 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000369331.8(CASP7):c.746G>A(p.Arg249Lys) variant causes a missense change. The variant allele was found at a frequency of 0.258 in 1,613,318 control chromosomes in the GnomAD database, including 55,255 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4392 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50863 hom. )

Consequence

CASP7
ENST00000369331.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.10

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026726127).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP7	NM_001227.5 linkuse as main transcript	c.780G>A	p.Gln260=	synonymous_variant	7/7	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8 linkuse as main transcript	c.780G>A	p.Gln260=	synonymous_variant	7/7	1	NM_001227.5	ENSP00000358324	P1	P55210-1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35146

AN:

151982

Hom.:

4386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.224

GnomAD3 exomes

AF:

0.261

AC:

65643

AN:

251410

Hom.:

8964

AF XY:

0.259

AC XY:

35182

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.417

Gnomad SAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.258

Gnomad OTH exome

AF:

0.258

GnomAD4 exome

AF:

0.260

AC:

380324

AN:

1461216

Hom.:

50863

Cov.:

AF XY:

0.259

AC XY:

188395

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.277

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.439

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.231

AC:

35166

AN:

152102

Hom.:

4392

Cov.:

AF XY:

0.232

AC XY:

17257

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.239

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.271

Gnomad4 NFE

AF:

0.262

Gnomad4 OTH

AF:

0.225

Alfa

AF:

0.239

Hom.:

6199

Bravo

AF:

0.226

TwinsUK

AF:

0.241

AC:

895

ALSPAC

AF:

0.266

AC:

1027

ESP6500AA

AF:

0.148

AC:

652

ESP6500EA

AF:

0.253

AC:

2173

ExAC

AF:

0.260

AC:

31503

Asia WGS

AF:

0.277

AC:

965

AN:

3478

EpiCase

AF:

0.250

EpiControl

AF:

0.245

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.3

DANN

Benign

0.95

Eigen

Benign

0.055

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.35

.;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

0.96

P;P;P;P;P;P

PROVEAN

Benign

0.060

N;.

REVEL

Benign

0.032

Sift

Benign

1.0

T;.

Polyphen

0.18

B;B

Vest4

0.24

ClinPred

0.012

GERP RS

4.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over