rs11593766

Variant names:

• chr10-113697505-T-G
• rs11555408
• NM_001227.5:c.12T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-113697505-T-G
• chr10-113697505-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/19 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 0.11 (860 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7870 hom.)
• Consequence: CASP7 NM_001227.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 21 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.12T>G	p.Asp4Glu	missense_variant	Exon 2 of 7	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.12T>G	p.Asp4Glu	missense_variant	Exon 2 of 7	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16098 AN: 152042 Hom.: 858 Cov.: 32

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

GnomAD2 exomes AF: 0.0952 AC: 23929 AN: 251318 AF XY: 0.0969

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 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.: 30 AF XY: 0.101 AC XY: 73398 AN XY: 724428

African (AFR) AF: 0.121 AC: 4050 AN: 33350

American (AMR) AF: 0.0669 AC: 2992 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3033 AN: 26090

East Asian (EAS) AF: 0.101 AC: 4004 AN: 39680

South Asian (SAS) AF: 0.101 AC: 8657 AN: 86118

European-Finnish (FIN) AF: 0.0695 AC: 3710 AN: 53414

Middle Eastern (MID) AF: 0.138 AC: 793 AN: 5758

European-Non Finnish (NFE) AF: 0.102 AC: 113108 AN: 1106294

Other (OTH) AF: 0.108 AC: 6474 AN: 60186

GnomAD4 genome AF: 0.106 AC: 16111 AN: 152160 Hom.: 860 Cov.: 32 AF XY: 0.104 AC XY: 7741 AN XY: 74416

African (AFR) AF: 0.121 AC: 5005 AN: 41500

American (AMR) AF: 0.0959 AC: 1467 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3470

East Asian (EAS) AF: 0.0889 AC: 461 AN: 5184

South Asian (SAS) AF: 0.0929 AC: 447 AN: 4810

European-Finnish (FIN) AF: 0.0692 AC: 734 AN: 10606

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7212 AN: 67982

Other (OTH) AF: 0.122 AC: 257 AN: 2104

Alfa AF: 0.104 Hom.: 2390

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	T
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	N
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	T
MutationAssessor	Uncertain	2.0	M;.;M;M;M;M;M;.
PhyloP100		0.0010
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	T
GERP RS		2.0
Varity_R		0.047
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11555408; hg19: chr10-115457264; COSMIC: COSV61881934;