rs11674246

chr2-201183400-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.-8+92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,926 control chromosomes in the GnomAD database, including 13,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (13665 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.138

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=-0.75).
• BP6: Variant 2-201183400-C-T is Benign according to our data. Variant chr2-201183400-C-T is described in ClinVar as [Benign]. Clinvar id is 1242631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP10	NM_032977.4	c.-8+92C>T		intron_variant		ENST00000286186.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP10	ENST00000286186.11	c.-8+92C>T		intron_variant		1	NM_032977.4	P2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63418 AN: 151808 Hom.: 13666 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.421

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.417 AC: 63425 AN: 151926 Hom.: 13665 Cov.: 32 AF XY: 0.412 AC XY: 30554 AN XY: 74228

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.420

Alfa AF: 0.453 Hom.: 2582

Bravo AF: 0.410

Asia WGS AF: 0.240 AC: 837 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

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	11
Dann	Benign	0.74

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: rs11674246; hg19: chr2-202048123;