dbSNP rs62339863: CASP3:c.-183+82T>G (chr4-184649313-A-C) – 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.-183+82T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 153,076 control chromosomes in the GnomAD database, including 7,079 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 0.29 ( 7025 hom., cov: 35)

Exomes 𝑓: 0.29 ( 54 hom. )

Consequence

CASP3
NM_004346.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.96

Publications

10 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP3	NM_004346.4 link	c.-183+82T>G		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.-183+82T>G		intron_variant	Intron 1 of 7	1	NM_004346.4	ENSP00000311032.4		P42574

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43404

AN:

151892

Hom.:

7020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.678

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.333

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.313

GnomAD4 exome

AF:

0.286

AC:

305

AN:

1066

Hom.:

AF XY:

0.268

AC XY:

175

AN XY:

654

show subpopulations

African (AFR)

AF:

0.143

AC:

AN:

American (AMR)

AF:

0.667

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.583

AC:

AN:

South Asian (SAS)

AF:

0.625

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AF:

0.188

AC:

AN:

European-Non Finnish (NFE)

AF:

0.246

AC:

197

AN:

802

Other (OTH)

AF:

0.283

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.286

AC:

43442

AN:

152010

Hom.:

7025

Cov.:

AF XY:

0.294

AC XY:

21847

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.189

AC:

7828

AN:

41504

American (AMR)

AF:

0.412

AC:

6297

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1047

AN:

3472

East Asian (EAS)

AF:

0.677

AC:

3473

AN:

5130

South Asian (SAS)

AF:

0.406

AC:

1961

AN:

4828

European-Finnish (FIN)

AF:

0.287

AC:

3037

AN:

10576

Middle Eastern (MID)

AF:

0.336

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.277

AC:

18794

AN:

67900

Other (OTH)

AF:

0.311

AC:

656

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1519

3037

4556

6074

7593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.270

Hom.:

710

Bravo

AF:

0.294

Asia WGS

AF:

0.502

AC:

1742

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.024

(source)

DANN

Benign

0.20

PhyloP100

-5.0

PromoterAI

-0.045

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

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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