chr10-113729492-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001227.5(CASP7):ā€‹c.864C>Gā€‹(p.Ile288Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000075 ( 0 hom. )

Consequence

CASP7
NM_001227.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.779
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CASP7NM_001227.5 linkuse as main transcriptc.864C>G p.Ile288Met missense_variant 7/7 ENST00000369318.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CASP7ENST00000369318.8 linkuse as main transcriptc.864C>G p.Ile288Met missense_variant 7/71 NM_001227.5 P1P55210-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251436
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461868
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 07, 2022The c.963C>G (p.I321M) alteration is located in exon 8 (coding exon 7) of the CASP7 gene. This alteration results from a C to G substitution at nucleotide position 963, causing the isoleucine (I) at amino acid position 321 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.015
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;T;T;T;T;.;.
Eigen
Benign
-0.058
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.42
N
LIST_S2
Uncertain
0.87
D;.;D;.;.;D;D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.46
T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.82
L;L;.;L;L;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-2.4
.;N;.;N;N;.;D
REVEL
Uncertain
0.32
Sift
Benign
0.080
.;T;.;T;T;.;T
Sift4G
Benign
0.082
T;T;T;T;T;T;T
Polyphen
1.0
D;D;.;D;D;D;.
Vest4
0.36
MutPred
0.73
Gain of disorder (P = 0.0168);Gain of disorder (P = 0.0168);.;Gain of disorder (P = 0.0168);Gain of disorder (P = 0.0168);.;.;
MVP
0.78
MPC
0.29
ClinPred
0.38
T
GERP RS
-1.3
Varity_R
0.53
gMVP
0.75

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.

Other links and lift over

dbSNP: rs751802124; hg19: chr10-115489251; API