dbSNP rs3787492: CTSZ:c.802-40C>T (chr20-58995799-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 NM_001336.4(CTSZ):c.802-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,576,296 control chromosomes in the GnomAD database, including 109,933 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 0.35 ( 9637 hom., cov: 31)

Exomes 𝑓: 0.37 ( 100296 hom. )

Consequence

CTSZ
NM_001336.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.254

Publications

3 publications found

Variant links:

Genes affected

CTSZ (HGNC:2547): (cathepsin Z) The protein encoded by this gene is a lysosomal cysteine proteinase and member of the peptidase C1 family. It exhibits both carboxy-monopeptidase and carboxy-dipeptidase activities. The encoded protein has also been known as cathepsin X and cathepsin P. This gene is expressed ubiquitously in cancer cell lines and primary tumors and, like other members of this family, may be involved in tumorigenesis. [provided by RefSeq, Oct 2008]

CTSZ 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSZ	NM_001336.4 link	c.802-40C>T		intron_variant	Intron 5 of 5	ENST00000217131.6	NP_001327.2	Q9UBR2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSZ	ENST00000217131.6 link	c.802-40C>T		intron_variant	Intron 5 of 5	1	NM_001336.4	ENSP00000217131.5		Q9UBR2

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52797

AN:

151798

Hom.:

9634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.328

GnomAD2 exomes

AF:

0.339

AC:

83252

AN:

245264

AF XY:

0.342

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.241

Gnomad ASJ exome

AF:

0.337

Gnomad EAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.491

Gnomad NFE exome

AF:

0.394

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.370

AC:

527549

AN:

1424378

Hom.:

100296

Cov.:

AF XY:

0.368

AC XY:

261702

AN XY:

710566

show subpopulations

African (AFR)

AF:

0.288

AC:

9418

AN:

32710

American (AMR)

AF:

0.244

AC:

10852

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

8808

AN:

25814

East Asian (EAS)

AF:

0.172

AC:

6774

AN:

39446

South Asian (SAS)

AF:

0.279

AC:

23811

AN:

85332

European-Finnish (FIN)

AF:

0.481

AC:

24768

AN:

51454

Middle Eastern (MID)

AF:

0.347

AC:

1913

AN:

5508

European-Non Finnish (NFE)

AF:

0.389

AC:

420431

AN:

1080464

Other (OTH)

AF:

0.351

AC:

20774

AN:

59154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

16104

32208

48311

64415

80519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12790

25580

38370

51160

63950

<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:

0.348

AC:

52812

AN:

151918

Hom.:

9637

Cov.:

AF XY:

0.350

AC XY:

25986

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.291

AC:

12057

AN:

41422

American (AMR)

AF:

0.283

AC:

4318

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1212

AN:

3468

East Asian (EAS)

AF:

0.174

AC:

900

AN:

5166

South Asian (SAS)

AF:

0.271

AC:

1301

AN:

4808

European-Finnish (FIN)

AF:

0.494

AC:

5208

AN:

10552

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.391

AC:

26585

AN:

67910

Other (OTH)

AF:

0.329

AC:

694

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1705

3410

5114

6819

8524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.363

Hom.:

14799

Bravo

AF:

0.329

Asia WGS

AF:

0.218

AC:

762

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.78

(source)

DANN

Benign

0.77

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