rs6435068

Positions:

• chr2-201211725-T-C

Variant summary

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

The NM_032977.4(CASP10):​c.1415+2163T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,188 control chromosomes in the GnomAD database, including 2,519 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 0.12 (2519 hom., cov: 32)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP10	NM_032977.4	c.1415+2163T>C		intron_variant		ENST00000286186.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP10	ENST00000286186.11	c.1415+2163T>C		intron_variant		1	NM_032977.4	P2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18813 AN: 152070 Hom.: 2498 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0571

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0886

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

GnomAD4 genome AF: 0.124 AC: 18889 AN: 152188 Hom.: 2519 Cov.: 32 AF XY: 0.121 AC XY: 8994 AN XY: 74424

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.0570

Gnomad4 ASJ AF: 0.0913

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0609

Gnomad4 FIN AF: 0.0327

Gnomad4 NFE AF: 0.0397

Gnomad4 OTH AF: 0.0962

Alfa AF: 0.0930 Hom.: 187

Bravo AF: 0.131

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
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: rs6435068; hg19: chr2-202076448;