Genetic Variant NM_001227.5:c.*351T>G (chr10-113729891-T-G) – 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.*351T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 231,012 control chromosomes in the GnomAD database, including 17,205 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 0.37 ( 10972 hom., cov: 32)

Exomes 𝑓: 0.39 ( 6233 hom. )

Consequence

CASP7
NM_001227.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.240

Publications

27 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=-0.87).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5 link	c.*351T>G		3_prime_UTR_variant	Exon 7 of 7	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.*351T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001227.5	ENSP00000358324.4		P55210-1

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56776

AN:

151932

Hom.:

10974

Cov.:

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.378

GnomAD4 exome

AF:

0.390

AC:

30805

AN:

78962

Hom.:

6233

Cov.:

AF XY:

0.389

AC XY:

15945

AN XY:

40938

show subpopulations

African (AFR)

AF:

0.461

AC:

1380

AN:

2996

American (AMR)

AF:

0.483

AC:

2177

AN:

4508

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

1145

AN:

2444

East Asian (EAS)

AF:

0.215

AC:

1025

AN:

4768

South Asian (SAS)

AF:

0.436

AC:

3229

AN:

7406

European-Finnish (FIN)

AF:

0.432

AC:

1394

AN:

3230

Middle Eastern (MID)

AF:

0.469

AC:

135

AN:

288

European-Non Finnish (NFE)

AF:

0.379

AC:

18486

AN:

48820

Other (OTH)

AF:

0.407

AC:

1834

AN:

4502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

881

1761

2642

3522

4403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

214

428

642

856

1070

<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:

0.374

AC:

56803

AN:

152050

Hom.:

10972

Cov.:

AF XY:

0.377

AC XY:

27990

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.429

AC:

17765

AN:

41456

American (AMR)

AF:

0.462

AC:

7060

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1485

AN:

3468

East Asian (EAS)

AF:

0.185

AC:

956

AN:

5172

South Asian (SAS)

AF:

0.377

AC:

1819

AN:

4822

European-Finnish (FIN)

AF:

0.382

AC:

4029

AN:

10558

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22527

AN:

67988

Other (OTH)

AF:

0.380

AC:

801

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1812

3624

5437

7249

9061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.352

Hom.:

15886

Bravo

AF:

0.382

Asia WGS

AF:

0.320

AC:

1112

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.9

(source)

DANN

Benign

0.50

PhyloP100

0.24

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