rs6750157

chr2-201208426-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.922+243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 963,430 control chromosomes in the GnomAD database, including 1,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (946 hom., cov: 31)
  • Exomes 𝑓: 0.0048 (391 hom.)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.79

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=-0.99).
• BP6: Variant 2-201208426-C-T is Benign according to our data. Variant chr2-201208426-C-T is described in ClinVar as [Benign]. Clinvar id is 1243974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP10	NM_032977.4	c.922+243C>T		intron_variant		ENST00000286186.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP10	ENST00000286186.11	c.922+243C>T		intron_variant		1	NM_032977.4	P2

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9344 AN: 151946 Hom.: 944 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0463

GnomAD4 exome AF: 0.00480 AC: 3891 AN: 811366 Hom.: 391 Cov.: 14 AF XY: 0.00442 AC XY: 1658 AN XY: 375420

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.0209

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000286

Gnomad4 SAS exome AF: 0.000375

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000245

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0616 AC: 9368 AN: 152064 Hom.: 946 Cov.: 31 AF XY: 0.0596 AC XY: 4429 AN XY: 74358

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0495 Hom.: 74

Bravo AF: 0.0697

Asia WGS AF: 0.0110 AC: 39 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

Feb 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.024
Dann	Benign	0.46

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: rs6750157; hg19: chr2-202073149;