NM_032977.4:c.1416-2001A>C

Variant names:

• chr2-201215587-A-C
• rs10931932
• NM_032977.4:c.1416-2001A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032977.4(CASP10):​c.1416-2001A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 152,010 control chromosomes in the GnomAD database, including 59,378 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 0.88 (59378 hom., cov: 29)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• autoimmune lymphoproliferative syndrome type 2A

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autoimmune lymphoproliferative syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP10	NM_032977.4	c.1416-2001A>C		intron_variant	Intron 9 of 9	ENST00000286186.11	NP_116759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP10	ENST00000286186.11	c.1416-2001A>C		intron_variant	Intron 9 of 9	1	NM_032977.4	ENSP00000286186.6

Frequencies

GnomAD3 genomes AF: 0.882 AC: 133995 AN: 151892 Hom.: 59334 Cov.: 29

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.971

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.882 AC: 134096 AN: 152010 Hom.: 59378 Cov.: 29 AF XY: 0.880 AC XY: 65377 AN XY: 74300

African (AFR) AF: 0.841 AC: 34832 AN: 41422

American (AMR) AF: 0.865 AC: 13193 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3238 AN: 3472

East Asian (EAS) AF: 0.848 AC: 4388 AN: 5176

South Asian (SAS) AF: 0.708 AC: 3407 AN: 4810

European-Finnish (FIN) AF: 0.971 AC: 10268 AN: 10580

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.911 AC: 61951 AN: 67992

Other (OTH) AF: 0.873 AC: 1842 AN: 2110

Alfa AF: 0.903 Hom.: 7254

Bravo AF: 0.874

Asia WGS AF: 0.753 AC: 2621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.32
DANN	Benign	0.76
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10931932; hg19: chr2-202080310;