Genetic Variant CASP7:c.-282G>C (chr10-113679771-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001267057.1(CASP7):c.17G>C(p.Arg6Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,304,694 control chromosomes in the GnomAD database, including 47,013 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 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 0.24 ( 4680 hom., cov: 33)

Exomes 𝑓: 0.27 ( 42333 hom. )

Consequence

CASP7
NM_001267057.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.21

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4609098E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5 link	c.-208G>C		upstream_gene_variant		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.-208G>C		upstream_gene_variant		1	NM_001227.5	ENSP00000358324.4		P55210-1

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36240

AN:

151990

Hom.:

4674

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.249

GnomAD3 exomes

AF:

0.311

AC:

6102

AN:

19630

Hom.:

1017

AF XY:

0.306

AC XY:

3302

AN XY:

10800

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.306

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.488

Gnomad SAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.285

GnomAD4 exome

AF:

0.266

AC:

306632

AN:

1152588

Hom.:

42333

Cov.:

AF XY:

0.266

AC XY:

147447

AN XY:

553608

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.299

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.290

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.260

GnomAD4 genome

AF:

0.238

AC:

36260

AN:

152106

Hom.:

4680

Cov.:

AF XY:

0.242

AC XY:

17975

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.182

Gnomad4 EAS

AF:

0.423

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.168

Hom.:

596

Bravo

AF:

0.234

TwinsUK

AF:

0.245

AC:

907

ALSPAC

AF:

0.264

AC:

1016

ExAC

AF:

0.171

AC:

2139

Asia WGS

AF:

0.322

AC:

1117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.37

DANN

Benign

0.40

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.00079

LIST_S2

Benign

0.33

MetaRNN

Benign

0.00015

PrimateAI

Uncertain

0.57

Vest4

0.10

GERP RS

-4.4

gMVP

0.10

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