rs7540874
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000680288.1(CTSS):c.*2859T>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 151,918 control chromosomes in the GnomAD database, including 11,574 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 0.38 ( 11574 hom., cov: 31)
Failed GnomAD Quality Control
Consequence
CTSS
ENST00000680288.1 3_prime_UTR
ENST00000680288.1 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.575
Genes affected
CTSS (HGNC:2545): (cathepsin S) The preproprotein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine proteinase that participates in the degradation of antigenic proteins to peptides for presentation on MHC class II molecules. The mature protein cleaves the invariant chain of MHC class II molecules in endolysosomal compartments and enables the formation of antigen-MHC class II complexes and the proper display of extracellular antigenic peptides by MHC-II. The mature protein also functions as an elastase over a broad pH range. When secreted from cells, this protein can remodel components of the extracellular matrix such as elastin, collagen, and fibronectin. This gene is implicated in the pathology of many inflammatory and autoimmune diseases and, given its elastase activity, plays a significant role in some pulmonary diseases. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTSS | NM_004079.5 | downstream_gene_variant | ENST00000368985.8 | NP_004070.3 | ||||
CTSS | NM_001199739.2 | downstream_gene_variant | NP_001186668.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTSS | ENST00000368985.8 | downstream_gene_variant | 1 | NM_004079.5 | ENSP00000357981 | P1 |
Frequencies
GnomAD3 genomes AF: 0.385 AC: 58415AN: 151800Hom.: 11564 Cov.: 31
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GnomAD4 exome Data not reliable, filtered out with message: AC0AC: 0AN: 0Hom.: 0 Cov.: 0AC XY: 0AN XY: 0
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GnomAD4 genome AF: 0.385 AC: 58443AN: 151918Hom.: 11574 Cov.: 31 AF XY: 0.389 AC XY: 28883AN XY: 74228
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ClinVar
Not reported inComputational scores
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at