1-150730241-G-C

Variant summary

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

The NM_004079.5(CTSS):c.*2805C>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 151,878 control chromosomes in the GnomAD database, including 11,593 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 0.39 (11593 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTSS NM_004079.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• 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	UniProt
CTSS	NM_004079.5	c.*2805C>G		3_prime_UTR_variant	8/8	ENST00000368985.8
CTSS	NM_001199739.2	c.*2805C>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSS	ENST00000368985.8	c.*2805C>G		3_prime_UTR_variant	8/8	1	NM_004079.5	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58470 AN: 151758 Hom.: 11583 Cov.: 31

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.393

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.385 AC: 58498 AN: 151878 Hom.: 11593 Cov.: 31 AF XY: 0.390 AC XY: 28923 AN XY: 74232

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.396

Alfa AF: 0.393 Hom.: 1588

Bravo AF: 0.377

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.52
Dann	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs1136808; hg19: chr1-150702717;