chr2-201208250-A-T

Position:

• chr2-201208250-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032977.4(CASP10):​c.922+67A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,551,694 control chromosomes in the GnomAD database, including 181 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 0.011 (20 hom., cov: 32)
  • Exomes 𝑓: 0.012 (161 hom.)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0119 (16638/1399456) while in subpopulation SAS AF= 0.0169 (1308/77228). AF 95% confidence interval is 0.0162. There are 161 homozygotes in gnomad4_exome. There are 8432 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1685 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP10	NM_032977.4	c.922+67A>T		intron_variant		ENST00000286186.11	NP_116759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP10	ENST00000286186.11	c.922+67A>T		intron_variant		1	NM_032977.4	ENSP00000286186.6

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1686 AN: 152120 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0163

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.0119 AC: 16638 AN: 1399456 Hom.: 161 Cov.: 30 AF XY: 0.0122 AC XY: 8432 AN XY: 692034

Gnomad4 AFR exome AF: 0.00129

Gnomad4 AMR exome AF: 0.00416

Gnomad4 ASJ exome AF: 0.0315

Gnomad4 EAS exome AF: 0.00118

Gnomad4 SAS exome AF: 0.0169

Gnomad4 FIN exome AF: 0.0518

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.0111 AC: 1685 AN: 152238 Hom.: 20 Cov.: 32 AF XY: 0.0127 AC XY: 947 AN XY: 74426

Gnomad4 AFR AF: 0.00193

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0161

Gnomad4 FIN AF: 0.0537

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00570 Hom.: 0

Bravo AF: 0.00752

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs41419046; hg19: chr2-202072973;