rs12613347

chr2-201190589-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032977.4(CASP10):c.442-2395C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,898 control chromosomes in the GnomAD database, including 3,411 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3411 hom., cov: 31)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

Genes affected

CASP10 (HGNC:1500): (caspase 10) 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 two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene are associated with type IIA autoimmune lymphoproliferative syndrome, non-Hodgkin lymphoma and gastric cancer. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP10	NM_032977.4	c.442-2395C>T		intron_variant		ENST00000286186.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP10	ENST00000286186.11	c.442-2395C>T		intron_variant		1	NM_032977.4	P2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29376 AN: 151780 Hom.: 3412 Cov.: 31

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29359 AN: 151898 Hom.: 3411 Cov.: 31 AF XY: 0.199 AC XY: 14758 AN XY: 74196

Gnomad4 AFR AF: 0.0706

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.201

Alfa AF: 0.223 Hom.: 5481

Bravo AF: 0.176

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.51
Dann	Benign	0.48

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: rs12613347; hg19: chr2-202055312;