Genetic Variant ENST00000345633.8:c.-282G>C (chr10-113679771-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000345633.8(CASP7):c.-282G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,304,694 control chromosomes in the GnomAD database, including 47,013 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 0.24 ( 4680 hom., cov: 33)

Exomes 𝑓: 0.27 ( 42333 hom. )

Consequence

CASP7
ENST00000345633.8 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.21

Publications

15 publications found

Variant links:

Genes affected

CASP7 (HGNC:1508): (caspase 7) This gene encodes 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 which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

CASP7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4609098E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5 link	c.-208G>C		upstream_gene_variant		ENST00000369318.8	NP_001218.1	P55210-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8 link	c.-208G>C		upstream_gene_variant		1	NM_001227.5	ENSP00000358324.4		P55210-1

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36240

AN:

151990

Hom.:

4674

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.249

GnomAD2 exomes

AF:

0.311

AC:

6102

AN:

19630

AF XY:

0.306

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.306

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.488

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.285

GnomAD4 exome

AF:

0.266

AC:

306632

AN:

1152588

Hom.:

42333

Cov.:

AF XY:

0.266

AC XY:

147447

AN XY:

553608

show subpopulations

African (AFR)

AF:

0.145

AC:

3456

AN:

23856

American (AMR)

AF:

0.299

AC:

4091

AN:

13684

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

3104

AN:

15932

East Asian (EAS)

AF:

0.463

AC:

12862

AN:

27768

South Asian (SAS)

AF:

0.289

AC:

12331

AN:

42694

European-Finnish (FIN)

AF:

0.290

AC:

7526

AN:

25954

Middle Eastern (MID)

AF:

0.240

AC:

758

AN:

3154

European-Non Finnish (NFE)

AF:

0.263

AC:

250361

AN:

952826

Other (OTH)

AF:

0.260

AC:

12143

AN:

46720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

10807

21614

32420

43227

54034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9482

18964

28446

37928

47410

<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:

0.238

AC:

36260

AN:

152106

Hom.:

4680

Cov.:

AF XY:

0.242

AC XY:

17975

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.150

AC:

6214

AN:

41546

American (AMR)

AF:

0.262

AC:

4006

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

630

AN:

3468

East Asian (EAS)

AF:

0.423

AC:

2171

AN:

5130

South Asian (SAS)

AF:

0.297

AC:

1429

AN:

4818

European-Finnish (FIN)

AF:

0.283

AC:

2990

AN:

10564

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17843

AN:

67964

Other (OTH)

AF:

0.251

AC:

530

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1397

2794

4190

5587

6984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.168

Hom.:

596

Bravo

AF:

0.234

TwinsUK

AF:

0.245

AC:

907

ALSPAC

AF:

0.264

AC:

1016

ExAC

AF:

0.171

AC:

2139

Asia WGS

AF:

0.322

AC:

1117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.37

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.00079

LIST_S2

Benign

0.33

MetaRNN

Benign

0.00015

PhyloP100

-2.2

PrimateAI

Uncertain

0.57

Vest4

0.10

GERP RS

-4.4

PromoterAI

-0.081

Neutral

(source)

gMVP

0.10

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