Genetic Variant CASP5:c.433+93G>C (chr11-105006990-C-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_004347.5(CASP5):c.433+93G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,031,102 control chromosomes in the GnomAD database, including 57,693 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 0.39 ( 12762 hom., cov: 32)

Exomes 𝑓: 0.31 ( 44931 hom. )

Consequence

CASP5
NM_004347.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.332

Publications

9 publications found

Variant links:

Genes affected

CASP5 (HGNC:1506): (caspase 5) This gene encodes 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. Overexpression of the active form of this enzyme induces apoptosis in fibroblasts. Max, a central component of the Myc/Max/Mad transcription regulation network important for cell growth, differentiation, and apoptosis, is cleaved by this protein; this process requires Fas-mediated dephosphorylation of Max. The expression of this gene is regulated by interferon-gamma and lipopolysaccharide. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]

CASP5 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP5	NM_004347.5 link	c.433+93G>C		intron_variant	Intron 3 of 9	ENST00000260315.8	NP_004338.3	P51878-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP5	ENST00000260315.8 link	c.433+93G>C		intron_variant	Intron 3 of 9	5	NM_004347.5	ENSP00000260315.3		P51878-1

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

59272

AN:

151902

Hom.:

12736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.585

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.258

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.341

GnomAD4 exome

AF:

0.313

AC:

275401

AN:

879082

Hom.:

44931

AF XY:

0.312

AC XY:

140583

AN XY:

450036

show subpopulations

African (AFR)

AF:

0.572

AC:

11566

AN:

20224

American (AMR)

AF:

0.218

AC:

6278

AN:

28830

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

4439

AN:

17326

East Asian (EAS)

AF:

0.237

AC:

8744

AN:

36824

South Asian (SAS)

AF:

0.257

AC:

15409

AN:

59906

European-Finnish (FIN)

AF:

0.304

AC:

13882

AN:

45702

Middle Eastern (MID)

AF:

0.184

AC:

806

AN:

4386

European-Non Finnish (NFE)

AF:

0.322

AC:

201474

AN:

625274

Other (OTH)

AF:

0.315

AC:

12803

AN:

40610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

9322

18644

27965

37287

46609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4870

9740

14610

19480

24350

<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:

0.390

AC:

59353

AN:

152020

Hom.:

12762

Cov.:

AF XY:

0.384

AC XY:

28529

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.585

AC:

24260

AN:

41440

American (AMR)

AF:

0.271

AC:

4140

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

918

AN:

3468

East Asian (EAS)

AF:

0.214

AC:

1110

AN:

5180

South Asian (SAS)

AF:

0.257

AC:

1239

AN:

4824

European-Finnish (FIN)

AF:

0.303

AC:

3196

AN:

10562

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.345

AC:

23454

AN:

67966

Other (OTH)

AF:

0.344

AC:

728

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1775

3551

5326

7102

8877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.219

Hom.:

459

Bravo

AF:

0.394

Asia WGS

AF:

0.286

AC:

994

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.41

(source)

DANN

Benign

0.26

PhyloP100

-0.33

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