dbSNP rs11593766: CASP7:p.Asp4Glu (chr10-113697505-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001227.5(CASP7):c.12T>G(p.Asp4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,607,744 control chromosomes in the GnomAD database, including 8,730 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.11 ( 860 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7870 hom. )

Consequence

CASP7
NM_001227.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00100

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=0.0017143488).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5 link	c.12T>G	p.Asp4Glu	missense_variant	Exon 2 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.12T>G	p.Asp4Glu	missense_variant	Exon 2 of 7	1	NM_001227.5	ENSP00000358324.4		P55210-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16098

AN:

152042

Hom.:

858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0961

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.0885

Gnomad SAS

AF:

0.0926

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.0952

AC:

23929

AN:

251318

Hom.:

1232

AF XY:

0.0969

AC XY:

13165

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.0646

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.0908

Gnomad SAS exome

AF:

0.0993

Gnomad FIN exome

AF:

0.0719

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.101

AC:

146821

AN:

1455584

Hom.:

7870

Cov.:

AF XY:

0.101

AC XY:

73398

AN XY:

724428

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.0669

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0695

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.106

AC:

16111

AN:

152160

Hom.:

860

Cov.:

AF XY:

0.104

AC XY:

7741

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.0959

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.0889

Gnomad4 SAS

AF:

0.0929

Gnomad4 FIN

AF:

0.0692

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.102

Hom.:

1586

Bravo

AF:

0.106

TwinsUK

AF:

0.103

AC:

383

ALSPAC

AF:

0.101

AC:

389

ESP6500AA

AF:

0.123

AC:

542

ESP6500EA

AF:

0.104

AC:

892

ExAC

AF:

0.0970

AC:

11780

Asia WGS

AF:

0.106

AC:

366

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.5

DANN

Benign

0.97

DEOGEN2

Benign

0.042

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

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.49

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

MetaRNN

Benign

0.0017

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

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;.;M;M;M;M;M;.

PROVEAN

Benign

-0.71

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

REVEL

Benign

0.018

Sift

Uncertain

0.0090

.;D;D;D;.;D;D;.

Sift4G

Benign

0.33

T;T;D;T;D;T;T;T

Polyphen

0.15

B;.;P;B;P;B;B;B

Vest4

0.17

MutPred

0.095

Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);.;

ClinPred

0.0039

GERP RS

2.0

Varity_R

0.047

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