rs1293288

Variant names:

• chr8-11861019-T-C
• rs1293288
• NM_001908.5:c.-26+6982A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-11861019-T-C
• chr8-11861019-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001908.5(CTSB):​c.-26+6982A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,100 control chromosomes in the GnomAD database, including 22,173 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 0.54 (22173 hom., cov: 33)
• Consequence: CTSB NM_001908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 27 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSB	NM_001908.5	c.-26+6982A>G		intron_variant	Intron 1 of 9	ENST00000353047.11	NP_001899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSB	ENST00000353047.11	c.-26+6982A>G		intron_variant	Intron 1 of 9	1	NM_001908.5	ENSP00000345672.5

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81948 AN: 151982 Hom.: 22150 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.522

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.539 AC: 82031 AN: 152100 Hom.: 22173 Cov.: 33 AF XY: 0.536 AC XY: 39831 AN XY: 74356

African (AFR) AF: 0.522 AC: 21654 AN: 41486

American (AMR) AF: 0.459 AC: 7008 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1752 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2645 AN: 5174

South Asian (SAS) AF: 0.549 AC: 2648 AN: 4822

European-Finnish (FIN) AF: 0.563 AC: 5954 AN: 10570

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38594 AN: 67988

Other (OTH) AF: 0.522 AC: 1100 AN: 2108

Alfa AF: 0.548 Hom.: 49457

Bravo AF: 0.530

Asia WGS AF: 0.521 AC: 1811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.038
DANN	Benign	0.84
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1293288; hg19: chr8-11718528;