rs3731714

chr2-201196097-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032977.4(CASP10):c.684+149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 626,684 control chromosomes in the GnomAD database, including 23,143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4558 hom., cov: 32)
  • Exomes 𝑓: 0.27 (18585 hom.)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.274

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-201196097-C-T is Benign according to our data. Variant chr2-201196097-C-T is described in ClinVar as [Benign]. Clinvar id is 1291086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP10	NM_032977.4	c.684+149C>T		intron_variant		ENST00000286186.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP10	ENST00000286186.11	c.684+149C>T		intron_variant		1	NM_032977.4	P2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33280 AN: 151912 Hom.: 4558 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.271 AC: 128455 AN: 474654 Hom.: 18585 AF XY: 0.267 AC XY: 67734 AN XY: 253298

Gnomad4 AFR exome AF: 0.0547

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.219 AC: 33277 AN: 152030 Hom.: 4558 Cov.: 32 AF XY: 0.217 AC XY: 16098 AN XY: 74326

Gnomad4 AFR AF: 0.0551

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.229

Alfa AF: 0.282 Hom.: 8719

Bravo AF: 0.207

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.1
Dann	Benign	0.78

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: rs3731714; hg19: chr2-202060820;