Genetic Variant CASP3:c.-182-16C>A (chr4-184648647-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004346.4(CASP3):c.-182-16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 155,138 control chromosomes in the GnomAD database, including 1,834 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 0.10 ( 1791 hom., cov: 32)

Exomes 𝑓: 0.12 ( 43 hom. )

Consequence

CASP3
NM_004346.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.78

Publications

16 publications found

Variant links:

Genes affected

CASP3 (HGNC:1504): (caspase 3) The protein encoded by this gene is a cysteine-aspartic acid protease that plays a central role in the execution-phase of cell apoptosis. The encoded protein cleaves and inactivates poly(ADP-ribose) polymerase while it cleaves and activates sterol regulatory element binding proteins as well as caspases 6, 7, and 9. This protein itself is processed by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. [provided by RefSeq, Aug 2017]

CASP3 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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP3	NM_004346.4 link	c.-182-16C>A		intron_variant	Intron 1 of 7	ENST00000308394.9	NP_004337.2	P42574

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP3	ENST00000308394.9 link	c.-182-16C>A		intron_variant	Intron 1 of 7	1	NM_004346.4	ENSP00000311032.4		P42574

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15538

AN:

152082

Hom.:

1790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0333

Gnomad AMI

AF:

0.0604

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.0718

Gnomad EAS

AF:

0.586

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.0861

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0748

Gnomad OTH

AF:

0.0962

GnomAD4 exome

AF:

0.124

AC:

364

AN:

2938

Hom.:

Cov.:

AF XY:

0.121

AC XY:

187

AN XY:

1544

show subpopulations

African (AFR)

AF:

0.0143

AC:

AN:

American (AMR)

AF:

0.237

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0854

AC:

AN:

East Asian (EAS)

AF:

0.448

AC:

146

AN:

326

South Asian (SAS)

AF:

0.118

AC:

AN:

European-Finnish (FIN)

AF:

0.0732

AC:

AN:

396

Middle Eastern (MID)

AF:

0.143

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0778

AC:

143

AN:

1838

Other (OTH)

AF:

0.164

AC:

AN:

140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

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:

0.102

AC:

15547

AN:

152200

Hom.:

1791

Cov.:

AF XY:

0.110

AC XY:

8186

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0332

AC:

1380

AN:

41548

American (AMR)

AF:

0.245

AC:

3746

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0718

AC:

249

AN:

3468

East Asian (EAS)

AF:

0.585

AC:

3017

AN:

5158

South Asian (SAS)

AF:

0.181

AC:

870

AN:

4816

European-Finnish (FIN)

AF:

0.0861

AC:

914

AN:

10610

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0748

AC:

5088

AN:

68002

Other (OTH)

AF:

0.0966

AC:

204

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

613

1225

1838

2450

3063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.0836

Hom.:

754

Bravo

AF:

0.116

Asia WGS

AF:

0.335

AC:

1161

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.8

(source)

DANN

Benign

0.84

PhyloP100

1.8

PromoterAI

-0.046

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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