rs753761002

Variant names:

• chr11-105029858-C-A
• rs753761002
• NM_001257118.3:c.669G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-105029858-C-A
• chr11-105029858-C-T

Variant summary

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

The NM_001257118.3(CASP1):​c.669G>T​(p.Glu223Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CASP1 NM_001257118.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

Genes affected

CASP1 (HGNC:1499): (caspase 1) This gene encodes a protein which is 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 2 subunits, large and small, that dimerize to form the active enzyme. This gene was identified by its ability to proteolytically cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the processes such as inflammation, septic shock, and wound healing. This gene has been shown to induce cell apoptosis and may function in various developmental stages. Studies of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]

LOC124902742 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP1	NM_001257118.3	c.669G>T	p.Glu223Asp	missense_variant	Exon 6 of 9	ENST00000533400.6	NP_001244047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP1	ENST00000533400.6	c.669G>T	p.Glu223Asp	missense_variant	Exon 6 of 9	1	NM_001257118.3	ENSP00000433138.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461510 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727082

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: 0.00000720

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;.;.;T;T;.;.;.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	T;T;T;.;T;T;D;.;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	.;.;.;L;L;.;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	D;D;N;N;N;D;D;D;N
REVEL	Benign	0.075
Sift	Benign	0.085	T;T;T;T;T;T;D;T;D
Sift4G	Benign	0.49	T;T;T;T;T;T;T;T;T
Polyphen		0.54, 0.10, 0.58, 0.99, 0.33, 0.38	.;P;B;P;P;D;B;D;B
Vest4		0.075, 0.15, 0.079, 0.13, 0.13, 0.064
MutPred		0.46		.;.;.;Loss of ubiquitination at K225 (P = 0.0747);Loss of ubiquitination at K225 (P = 0.0747);.;.;.;.;
MVP		0.73
MPC		0.34
ClinPred		0.95	D
GERP RS		0.14
Varity_R		0.61
gMVP		0.28

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

Other links and lift over

dbSNP: rs753761002; hg19: chr11-104900585;