dbSNP rs556205: CASP1:c.1007-330A>C (chr11-105027281-T-G) – 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.1007-330A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 529,358 control chromosomes in the GnomAD database, including 3,222 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 0.095 ( 975 hom., cov: 32)

Exomes 𝑓: 0.10 ( 2247 hom. )

Consequence

CASP1
NM_001257118.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.307

Publications

4 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:

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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=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP1	NM_001257118.3 link	c.1007-330A>C		intron_variant	Intron 7 of 8	ENST00000533400.6	NP_001244047.1	P29466-1A8K249

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP1	ENST00000533400.6 link	c.1007-330A>C		intron_variant	Intron 7 of 8	1	NM_001257118.3	ENSP00000433138.1		P29466-1

Frequencies

GnomAD3 genomes

AF:

0.0946

AC:

14379

AN:

151998

Hom.:

972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0311

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.0996

AC:

37567

AN:

377242

Hom.:

2247

AF XY:

0.0989

AC XY:

19565

AN XY:

197830

show subpopulations

African (AFR)

AF:

0.0301

AC:

329

AN:

10946

American (AMR)

AF:

0.240

AC:

3147

AN:

13122

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

1324

AN:

12092

East Asian (EAS)

AF:

0.00126

AC:

AN:

27776

South Asian (SAS)

AF:

0.0925

AC:

3149

AN:

34042

European-Finnish (FIN)

AF:

0.137

AC:

3415

AN:

24946

Middle Eastern (MID)

AF:

0.117

AC:

202

AN:

1732

European-Non Finnish (NFE)

AF:

0.103

AC:

23701

AN:

229902

Other (OTH)

AF:

0.0999

AC:

2265

AN:

22684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1548

3096

4645

6193

7741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<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:

0.0946

AC:

14393

AN:

152116

Hom.:

975

Cov.:

AF XY:

0.0993

AC XY:

7386

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0314

AC:

1303

AN:

41550

American (AMR)

AF:

0.214

AC:

3258

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

369

AN:

3468

East Asian (EAS)

AF:

0.00444

AC:

AN:

5180

South Asian (SAS)

AF:

0.101

AC:

488

AN:

4824

European-Finnish (FIN)

AF:

0.142

AC:

1501

AN:

10600

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7057

AN:

67946

Other (OTH)

AF:

0.113

AC:

237

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

664

1328

1992

2656

3320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.104

Hom.:

308

Bravo

AF:

0.0981

Asia WGS

AF:

0.0640

AC:

220

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.71

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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