dbSNP rs59760601: CASP3:c.-174C>T (chr4-184644689-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000393585.6(CASP3):c.-174C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 354,102 control chromosomes in the GnomAD database, including 8,999 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 0.17 ( 3205 hom., cov: 32)

Exomes 𝑓: 0.20 ( 5794 hom. )

Consequence

CASP3
ENST00000393585.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253

Publications

1 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP3	NM_004346.4 link	c.-16+3776C>T		intron_variant	Intron 2 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.-16+3776C>T		intron_variant	Intron 2 of 7	1	NM_004346.4	ENSP00000311032.4		P42574

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25746

AN:

151958

Hom.:

3201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.678

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.159

GnomAD4 exome

AF:

0.203

AC:

41107

AN:

202026

Hom.:

5794

Cov.:

AF XY:

0.210

AC XY:

24344

AN XY:

116186

show subpopulations

African (AFR)

AF:

0.119

AC:

539

AN:

4544

American (AMR)

AF:

0.365

AC:

4843

AN:

13276

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

914

AN:

6466

East Asian (EAS)

AF:

0.696

AC:

4670

AN:

6710

South Asian (SAS)

AF:

0.289

AC:

11235

AN:

38820

European-Finnish (FIN)

AF:

0.141

AC:

3141

AN:

22270

Middle Eastern (MID)

AF:

0.131

AC:

AN:

700

European-Non Finnish (NFE)

AF:

0.140

AC:

14045

AN:

100498

Other (OTH)

AF:

0.186

AC:

1628

AN:

8742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1314

2629

3943

5258

6572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<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:

0.169

AC:

25763

AN:

152076

Hom.:

3205

Cov.:

AF XY:

0.177

AC XY:

13181

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.110

AC:

4573

AN:

41486

American (AMR)

AF:

0.297

AC:

4529

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

510

AN:

3472

East Asian (EAS)

AF:

0.678

AC:

3502

AN:

5168

South Asian (SAS)

AF:

0.301

AC:

1451

AN:

4818

European-Finnish (FIN)

AF:

0.140

AC:

1481

AN:

10556

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9213

AN:

67998

Other (OTH)

AF:

0.160

AC:

337

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

973

1946

2920

3893

4866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<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:

0.143

Hom.:

211

Bravo

AF:

0.181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.7

(source)

DANN

Benign

0.84

PhyloP100

-0.25

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