chr8-11845033-T-C

Position:

• chr8-11845033-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000353047.11(CTSB):​c.*92A>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 0.385 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 ENST00000353047.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CTSB	NM_001908.5	c.*92A>G		3_prime_UTR_variant	10/10	ENST00000353047.11	NP_001899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSB	ENST00000353047.11	c.*92A>G		3_prime_UTR_variant	10/10	1	NM_001908.5	ENSP00000345672	P3

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

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.541

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.367

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

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.363

Alfa AF: 0.359 Hom.: 12470

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs8898; hg19: chr8-11702542;