rs55901059

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001225.4(CASP4):c.852G>T(p.Glu284Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,611,450 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 80 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 54 hom. )

Consequence

CASP4
NM_001225.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.04

Publications

6 publications found

Variant links:

Genes affected

CASP4 (HGNC:1505): (caspase 4) This gene encodes a protein that 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 composed of a prodomain and a large and small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This caspase is able to cleave and activate its own precursor protein, as well as caspase 1 precursor. When overexpressed, this gene induces cell apoptosis. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

CASP4 links:

ENSG00000303891 (HGNC:):

ENSG00000303891 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003347814).

BP6

Variant 11-104948606-C-A is Benign according to our data. Variant chr11-104948606-C-A is described in ClinVar as Benign. ClinVar VariationId is 787387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001225.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP4	NM_001225.4	MANE Select	c.852G>T	p.Glu284Asp	missense	Exon 6 of 9	NP_001216.1	P49662-1
	CASP4	NM_033306.3		c.684G>T	p.Glu228Asp	missense	Exon 7 of 10	NP_150649.1	P49662-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CASP4	ENST00000444739.7	TSL:1 MANE Select	c.852G>T	p.Glu284Asp	missense	Exon 6 of 9	ENSP00000388566.2	P49662-1
CASP4	ENST00000393150.7	TSL:1	c.684G>T	p.Glu228Asp	missense	Exon 6 of 9	ENSP00000376857.3	P49662-2
CASP4	ENST00000533730.5	TSL:1	n.932G>T		non_coding_transcript_exon	Exon 6 of 8

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2599

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00452

AC:

1131

AN:

250406

AF XY:

0.00307

show subpopulations

Gnomad AFR exome

AF:

0.0649

Gnomad AMR exome

AF:

0.00167

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000987

GnomAD4 exome

AF:

0.00169

AC:

2464

AN:

1459176

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1020

AN XY:

725806

show subpopulations

African (AFR)

AF:

0.0620

AC:

2070

AN:

33380

American (AMR)

AF:

0.00211

AC:

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000817

AC:

AN:

85718

European-Finnish (FIN)

AF:

0.0000750

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000495

AC:

AN:

1110462

Other (OTH)

AF:

0.00365

AC:

220

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

107

215

322

430

537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.0171

AC:

2604

AN:

152274

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1196

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0601

AC:

2499

AN:

41554

American (AMR)

AF:

0.00451

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68022

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

114

228

343

457

571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00304

Hom.:

Bravo

AF:

0.0191

ESP6500AA

AF:

0.0652

AC:

287

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00584

AC:

709

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.084

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.088

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

PhyloP100

-2.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

REVEL

Benign

0.020

Sift

Benign

0.16

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.058

MVP

0.12

MPC

0.065

ClinPred

0.0099

GERP RS

-2.6

Varity_R

0.091

gMVP

0.34

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over