dbSNP rs1296023: CTSB:c.-457T>C (chr8-11869308-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000534382.6(CTSB):c.-457T>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 0.325 in 149,306 control chromosomes in the GnomAD database, including 7,936 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 0.33 ( 7929 hom., cov: 27)

Exomes 𝑓: 0.35 ( 7 hom. )

Consequence

CTSB
ENST00000534382.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.339

Publications

18 publications found

Variant links:

Genes affected

CTSB (HGNC:2527): (cathepsin B) This gene encodes a member of the C1 family of peptidases. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the cathepsin B light and heavy chains, which can dimerize to form the double chain form of the enzyme. This enzyme is a lysosomal cysteine protease with both endopeptidase and exopeptidase activity that may play a role in protein turnover. It is also known as amyloid precursor protein secretase and is involved in the proteolytic processing of amyloid precursor protein (APP). Incomplete proteolytic processing of APP has been suggested to be a causative factor in Alzheimer's disease, the most common cause of dementia. Overexpression of the encoded protein has been associated with esophageal adenocarcinoma and other tumors. Both Cathepsin B and Cathepsin L are involved in the cleavage of the spike protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon its entry to the human host cell. Multiple pseudogenes of this gene have been identified. [provided by RefSeq, Sep 2020]

CTSB Gene-Disease associations (from GenCC):

keratolytic winter erythema
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

CTSB 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 (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSB	ENST00000534382.6 link	c.-457T>C		5_prime_UTR_variant	Exon 1 of 10	4		ENSP00000435260.2		P07858E9PKX0
CTSB	ENST00000677671.1 link	c.-412T>C		5_prime_UTR_variant	Exon 1 of 10			ENSP00000503578.1		P07858

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

48500

AN:

149110

Hom.:

7930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.484

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.281

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.312

GnomAD4 exome

AF:

0.347

AC:

AN:

Hom.:

Cov.:

AF XY:

0.368

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.350

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.325

AC:

48532

AN:

149208

Hom.:

7929

Cov.:

AF XY:

0.327

AC XY:

23764

AN XY:

72686

show subpopulations

African (AFR)

AF:

0.318

AC:

12836

AN:

40414

American (AMR)

AF:

0.305

AC:

4578

AN:

15022

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

748

AN:

3458

East Asian (EAS)

AF:

0.485

AC:

2413

AN:

4976

South Asian (SAS)

AF:

0.366

AC:

1729

AN:

4722

European-Finnish (FIN)

AF:

0.356

AC:

3556

AN:

9998

Middle Eastern (MID)

AF:

0.275

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.320

AC:

21569

AN:

67376

Other (OTH)

AF:

0.314

AC:

648

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1575

3151

4726

6302

7877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.317

Hom.:

27800

Bravo

AF:

0.318

Asia WGS

AF:

0.413

AC:

1436

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.5

(source)

DANN

Benign

0.56

PhyloP100

0.34

PromoterAI

0.010

Neutral

(source)

Splicing

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