dbSNP rs11226565: CASP4:c.926-374T>C (chr11-104947566-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 NM_001225.4(CASP4):c.926-374T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 154,278 control chromosomes in the GnomAD database, including 4,283 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 0.23 ( 4230 hom., cov: 32)

Exomes 𝑓: 0.20 ( 53 hom. )

Consequence

CASP4
NM_001225.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.854

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CASP4	NM_001225.4 link	c.926-374T>C	intron_variant	Intron 6 of 8	ENST00000444739.7	NP_001216.1	P49662-1
CASP4	NM_033306.3 link	c.758-374T>C	intron_variant	Intron 7 of 9		NP_150649.1	P49662-2
CASP4	XM_011543019.2 link	c.653-374T>C	intron_variant	Intron 5 of 7		XP_011541321.1	P49662

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP4	ENST00000444739.7 link	c.926-374T>C		intron_variant	Intron 6 of 8	1	NM_001225.4	ENSP00000388566.2		P49662-1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34795

AN:

151974

Hom.:

4223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.0905

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.204

AC:

447

AN:

2186

Hom.:

Cov.:

AF XY:

0.214

AC XY:

255

AN XY:

1190

show subpopulations

African (AFR)

AF:

0.300

AC:

AN:

American (AMR)

AF:

0.278

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

AN:

East Asian (EAS)

AF:

0.0625

AC:

AN:

South Asian (SAS)

AF:

0.205

AC:

AN:

European-Finnish (FIN)

AF:

0.235

AC:

AN:

Middle Eastern (MID)

AF:

0.417

AC:

AN:

European-Non Finnish (NFE)

AF:

0.203

AC:

325

AN:

1598

Other (OTH)

AF:

0.169

AC:

AN:

130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.229

AC:

34837

AN:

152092

Hom.:

4230

Cov.:

AF XY:

0.232

AC XY:

17280

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.250

AC:

10364

AN:

41520

American (AMR)

AF:

0.279

AC:

4266

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

661

AN:

3466

East Asian (EAS)

AF:

0.0903

AC:

468

AN:

5182

South Asian (SAS)

AF:

0.209

AC:

1008

AN:

4814

European-Finnish (FIN)

AF:

0.292

AC:

3085

AN:

10570

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14202

AN:

67964

Other (OTH)

AF:

0.233

AC:

492

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1374

2748

4122

5496

6870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.216

Hom.:

8173

Bravo

AF:

0.233

Asia WGS

AF:

0.175

AC:

606

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.7

(source)

DANN

Benign

0.80

PhyloP100

0.85

PromoterAI

-0.11

Neutral

(source)

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

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