dbSNP rs2282659: CASP1:n.*736T>C (chr11-105026710-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000529871.1(CASP1):n.*736T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 639,318 control chromosomes in the GnomAD database, including 21,171 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 0.24 ( 4600 hom., cov: 32)

Exomes 𝑓: 0.26 ( 16571 hom. )

Consequence

CASP1
ENST00000529871.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

15 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP1	NM_001257118.3 link	c.1116+132T>C		intron_variant	Intron 8 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.1116+132T>C		intron_variant	Intron 8 of 8	1	NM_001257118.3	ENSP00000433138.1		P29466-1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36643

AN:

151732

Hom.:

4596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.214

GnomAD4 exome

AF:

0.256

AC:

124953

AN:

487470

Hom.:

16571

Cov.:

AF XY:

0.256

AC XY:

66891

AN XY:

260914

show subpopulations

African (AFR)

AF:

0.199

AC:

2598

AN:

13048

American (AMR)

AF:

0.175

AC:

3944

AN:

22480

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

2900

AN:

14608

East Asian (EAS)

AF:

0.260

AC:

8323

AN:

32046

South Asian (SAS)

AF:

0.222

AC:

10856

AN:

48836

European-Finnish (FIN)

AF:

0.226

AC:

7946

AN:

35136

Middle Eastern (MID)

AF:

0.158

AC:

340

AN:

2158

European-Non Finnish (NFE)

AF:

0.278

AC:

81228

AN:

291664

Other (OTH)

AF:

0.248

AC:

6818

AN:

27494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5133

10266

15398

20531

25664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.241

AC:

36665

AN:

151848

Hom.:

4600

Cov.:

AF XY:

0.240

AC XY:

17815

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.207

AC:

8584

AN:

41436

American (AMR)

AF:

0.197

AC:

2993

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

697

AN:

3466

East Asian (EAS)

AF:

0.249

AC:

1280

AN:

5148

South Asian (SAS)

AF:

0.220

AC:

1059

AN:

4804

European-Finnish (FIN)

AF:

0.226

AC:

2384

AN:

10542

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

19051

AN:

67920

Other (OTH)

AF:

0.219

AC:

462

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1427

2854

4280

5707

7134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.263

Hom.:

21330

Bravo

AF:

0.234

Asia WGS

AF:

0.266

AC:

923

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.23

(source)

DANN

Benign

0.57

PhyloP100

-1.1

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