ENST00000531551.5:n.*660A>G

Variant names:

• chr8-11845033-T-C
• rs8898
• ENST00000531551.5:n.*660A>G

Variant summary

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

The ENST00000531551.5(CTSB):​n.*660A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 874,710 control chromosomes in the GnomAD database, including 66,822 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 (10844 hom., cov: 32)
  • Exomes 𝑓: 0.39 (55978 hom.)
• Consequence: CTSB ENST00000531551.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889
• Publications: 21 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSB	NM_001908.5	c.*92A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000353047.11	NP_001899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSB	ENST00000353047.11	c.*92A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_001908.5	ENSP00000345672.5

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56756 AN: 151834 Hom.: 10847 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.387 AC: 279684 AN: 722760 Hom.: 55978 Cov.: 9 AF XY: 0.389 AC XY: 147159 AN XY: 378280

African (AFR) AF: 0.322 AC: 6034 AN: 18734

American (AMR) AF: 0.503 AC: 17846 AN: 35446

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 6925 AN: 20054

East Asian (EAS) AF: 0.541 AC: 18059 AN: 33368

South Asian (SAS) AF: 0.473 AC: 30840 AN: 65190

European-Finnish (FIN) AF: 0.472 AC: 20017 AN: 42416

Middle Eastern (MID) AF: 0.358 AC: 1069 AN: 2984

European-Non Finnish (NFE) AF: 0.354 AC: 165795 AN: 468866

Other (OTH) AF: 0.367 AC: 13099 AN: 35702

GnomAD4 genome AF: 0.374 AC: 56777 AN: 151950 Hom.: 10844 Cov.: 32 AF XY: 0.382 AC XY: 28382 AN XY: 74254

African (AFR) AF: 0.321 AC: 13308 AN: 41430

American (AMR) AF: 0.444 AC: 6790 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3470

East Asian (EAS) AF: 0.531 AC: 2736 AN: 5154

South Asian (SAS) AF: 0.481 AC: 2315 AN: 4808

European-Finnish (FIN) AF: 0.484 AC: 5114 AN: 10562

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24166 AN: 67942

Other (OTH) AF: 0.363 AC: 763 AN: 2104

Alfa AF: 0.359 Hom.: 18208

Bravo AF: 0.368

Asia WGS AF: 0.482 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8898; hg19: chr8-11702542;