rs12613347

Variant names:

• chr2-201190589-C-T
• rs12613347
• NM_032977.4:c.442-2395C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

CASP10 Gene-Disease associations (from GenCC):

• autoimmune lymphoproliferative syndrome type 2A

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autoimmune lymphoproliferative syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP10	NM_032977.4	MANE Select	c.442-2395C>T		intron	N/A	NP_116759.2
	CASP10	NM_032974.5		c.442-2395C>T		intron	N/A	NP_116756.2
	CASP10	NM_001230.5		c.442-2395C>T		intron	N/A	NP_001221.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP10	ENST00000286186.11	TSL:1 MANE Select	c.442-2395C>T		intron	N/A	ENSP00000286186.6
	CASP10	ENST00000448480.1	TSL:1	c.442-2395C>T		intron	N/A	ENSP00000396835.1
	CASP10	ENST00000313728.12	TSL:1	c.442-2395C>T		intron	N/A	ENSP00000314599.7

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

African (AFR) AF: 0.0706 AC: 2929 AN: 41458

American (AMR) AF: 0.163 AC: 2483 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 956 AN: 3466

East Asian (EAS) AF: 0.341 AC: 1755 AN: 5142

South Asian (SAS) AF: 0.311 AC: 1493 AN: 4808

European-Finnish (FIN) AF: 0.331 AC: 3493 AN: 10538

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15509 AN: 67956

Other (OTH) AF: 0.201 AC: 421 AN: 2098

Alfa AF: 0.210 Hom.: 7543

Bravo AF: 0.176

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.51
DANN	Benign	0.48
PhyloP100		-1.8
Mutation Taster		=100/0	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: rs12613347; hg19: chr2-202055312;