Genetic Variant CASP1:c.274+365T>G (chr11-105033843-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001257118.3(CASP1):c.274+365T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 573,094 control chromosomes in the GnomAD database, including 9,467 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 0.18 ( 2539 hom., cov: 32)

Exomes 𝑓: 0.17 ( 6928 hom. )

Consequence

CASP1
NM_001257118.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.499

Publications

8 publications found

Variant links:

Genes affected

CASP1 (HGNC:1499): (caspase 1) 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 2 subunits, large and small, that dimerize to form the active enzyme. This gene was identified by its ability to proteolytically cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the processes such as inflammation, septic shock, and wound healing. This gene has been shown to induce cell apoptosis and may function in various developmental stages. Studies of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]

CASP1 links:

ENSG00000303891 (HGNC:):

ENSG00000303891 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=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP1	NM_001257118.3 link	c.274+365T>G		intron_variant	Intron 2 of 8	ENST00000533400.6	NP_001244047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP1	ENST00000533400.6 link	c.274+365T>G		intron_variant	Intron 2 of 8	1	NM_001257118.3	ENSP00000433138.1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26719

AN:

152086

Hom.:

2537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.00423

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.167

AC:

70122

AN:

420890

Hom.:

6928

AF XY:

0.159

AC XY:

37691

AN XY:

237256

show subpopulations

African (AFR)

AF:

0.178

AC:

2176

AN:

12242

American (AMR)

AF:

0.329

AC:

11261

AN:

34262

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

2290

AN:

13798

East Asian (EAS)

AF:

0.00207

AC:

AN:

18332

South Asian (SAS)

AF:

0.108

AC:

7025

AN:

64822

European-Finnish (FIN)

AF:

0.217

AC:

4411

AN:

20292

Middle Eastern (MID)

AF:

0.105

AC:

328

AN:

3132

European-Non Finnish (NFE)

AF:

0.168

AC:

39235

AN:

233286

Other (OTH)

AF:

0.162

AC:

3358

AN:

20724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2856

5712

8568

11424

14280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.176

AC:

26740

AN:

152204

Hom.:

2539

Cov.:

AF XY:

0.177

AC XY:

13150

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.178

AC:

7401

AN:

41532

American (AMR)

AF:

0.254

AC:

3887

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

571

AN:

3470

East Asian (EAS)

AF:

0.00444

AC:

AN:

5186

South Asian (SAS)

AF:

0.112

AC:

539

AN:

4826

European-Finnish (FIN)

AF:

0.217

AC:

2294

AN:

10582

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11335

AN:

68006

Other (OTH)

AF:

0.182

AC:

385

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1118

2235

3353

4470

5588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.169

Hom.:

3969

Bravo

AF:

0.181

Asia WGS

AF:

0.0760

AC:

262

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

(source)

DANN

Benign

0.48

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over