Genetic Variant CASP7:c.247+91C>T (chr10-113721259-C-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_001227.5(CASP7):c.247+91C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,328,686 control chromosomes in the GnomAD database, including 46,378 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 ( 4451 hom., cov: 32)

Exomes 𝑓: 0.26 ( 41927 hom. )

Consequence

CASP7
NM_001227.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.748

Publications

47 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 (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5 link	c.247+91C>T		intron_variant	Intron 3 of 6	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8 link	c.247+91C>T		intron_variant	Intron 3 of 6	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35301

AN:

151966

Hom.:

4448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.391

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.242

GnomAD4 exome

AF:

0.261

AC:

307158

AN:

1176604

Hom.:

41927

AF XY:

0.261

AC XY:

152747

AN XY:

586338

show subpopulations

African (AFR)

AF:

0.134

AC:

3539

AN:

26440

American (AMR)

AF:

0.283

AC:

8784

AN:

31054

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

3690

AN:

19290

East Asian (EAS)

AF:

0.436

AC:

16613

AN:

38060

South Asian (SAS)

AF:

0.263

AC:

17226

AN:

65544

European-Finnish (FIN)

AF:

0.271

AC:

13501

AN:

49876

Middle Eastern (MID)

AF:

0.264

AC:

1305

AN:

4948

European-Non Finnish (NFE)

AF:

0.258

AC:

229864

AN:

891392

Other (OTH)

AF:

0.253

AC:

12636

AN:

50000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

10850

21700

32550

43400

54250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7472

14944

22416

29888

37360

<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:

0.232

AC:

35314

AN:

152082

Hom.:

4451

Cov.:

AF XY:

0.234

AC XY:

17407

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.140

AC:

5810

AN:

41514

American (AMR)

AF:

0.254

AC:

3875

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

639

AN:

3472

East Asian (EAS)

AF:

0.415

AC:

2140

AN:

5162

South Asian (SAS)

AF:

0.271

AC:

1304

AN:

4810

European-Finnish (FIN)

AF:

0.270

AC:

2853

AN:

10578

Middle Eastern (MID)

AF:

0.248

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.261

AC:

17749

AN:

67990

Other (OTH)

AF:

0.244

AC:

516

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1382

2764

4145

5527

6909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.258

Hom.:

16299

Bravo

AF:

0.228

Asia WGS

AF:

0.302

AC:

1049

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.96

(source)

DANN

Benign

0.57

PhyloP100

-0.75

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