rs11204722

Positions:

• chr1-150757708-C-A
• chr1-150757708-C-T

Variant summary

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

The NM_004079.5(CTSS):​c.249+150G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 596,812 control chromosomes in the GnomAD database, including 39,730 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 0.35 (9761 hom., cov: 31)
  • Exomes 𝑓: 0.36 (29969 hom.)
• Consequence: CTSS NM_004079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSS	NM_004079.5	c.249+150G>T		intron_variant		ENST00000368985.8
CTSS	NM_001199739.2	c.249+150G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSS	ENST00000368985.8	c.249+150G>T		intron_variant		1	NM_004079.5	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53421 AN: 151860 Hom.: 9755 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.361 AC: 160608 AN: 444834 Hom.: 29969 AF XY: 0.364 AC XY: 81731 AN XY: 224558

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.466

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.495

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.372

GnomAD4 genome AF: 0.352 AC: 53444 AN: 151978 Hom.: 9761 Cov.: 31 AF XY: 0.357 AC XY: 26495 AN XY: 74272

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.363

Alfa AF: 0.222 Hom.: 531

Bravo AF: 0.347

Asia WGS AF: 0.385 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.65
DANN	Benign	0.53

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: rs11204722; hg19: chr1-150730184;