Genetic Variant ENST00000448480.1:c.1287-6991G>A (chr2-201221942-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000448480.1(CASP10):c.1287-6991G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,250 control chromosomes in the GnomAD database, including 213 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 0.045 ( 213 hom., cov: 32)

Consequence

CASP10
ENST00000448480.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.279

Publications

3 publications found

Variant links:

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

CASP10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP10	NM_032974.5 link	c.1416-6991G>A		intron_variant	Intron 9 of 9		NP_116756.2	Q92851-1
CASP10	NM_001206542.2 link	c.1287-6991G>A		intron_variant	Intron 7 of 7		NP_001193471.1	Q92851-5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CASP10	ENST00000448480.1 link	c.1287-6991G>A	intron_variant	Intron 7 of 7	1	ENSP00000396835.1	Q92851-5
CASP10	ENST00000272879.9 link	c.1416-6991G>A	intron_variant	Intron 9 of 9	2	ENSP00000272879.5	Q92851-1
CASP10	ENST00000696199.1 link	c.722-6988G>A	intron_variant	Intron 6 of 6		ENSP00000512481.1	A0A8Q3WLN0

Frequencies

GnomAD3 genomes

AF:

0.0447

AC:

6798

AN:

152132

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0563

Gnomad ASJ

AF:

0.0501

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00912

Gnomad FIN

AF:

0.0393

Gnomad MID

AF:

0.0613

Gnomad NFE

AF:

0.0682

Gnomad OTH

AF:

0.0522

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

GnomAD4 genome

AF:

0.0447

AC:

6799

AN:

152250

Hom.:

213

Cov.:

AF XY:

0.0431

AC XY:

3205

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0118

AC:

492

AN:

41564

American (AMR)

AF:

0.0563

AC:

860

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0501

AC:

174

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.00892

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0393

AC:

417

AN:

10608

Middle Eastern (MID)

AF:

0.0660

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0683

AC:

4643

AN:

68008

Other (OTH)

AF:

0.0511

AC:

108

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

313

626

939

1252

1565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0563

Hom.:

107

Bravo

AF:

0.0457

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.58

(source)

DANN

Benign

0.41

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over