rs11204722

Variant names:

• chr1-150757708-C-A
• rs11204722
• NM_004079.5:c.249+150G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004079.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSS	NM_004079.5	MANE Select	c.249+150G>T		intron	N/A	NP_004070.3
	CTSS	NM_001199739.2		c.249+150G>T		intron	N/A	NP_001186668.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSS	ENST00000368985.8	TSL:1 MANE Select	c.249+150G>T		intron	N/A	ENSP00000357981.3
	CTSS	ENST00000681863.1		n.547G>T		non_coding_transcript_exon	Exon 3 of 3
	CTSS	ENST00000679512.1		c.249+150G>T		intron	N/A	ENSP00000505113.1

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

African (AFR) AF: 0.271 AC: 3387 AN: 12520

American (AMR) AF: 0.391 AC: 5208 AN: 13308

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 5183 AN: 11112

East Asian (EAS) AF: 0.366 AC: 9903 AN: 27060

South Asian (SAS) AF: 0.495 AC: 8216 AN: 16594

European-Finnish (FIN) AF: 0.349 AC: 10025 AN: 28694

Middle Eastern (MID) AF: 0.422 AC: 845 AN: 2000

European-Non Finnish (NFE) AF: 0.352 AC: 109255 AN: 310468

Other (OTH) AF: 0.372 AC: 8586 AN: 23078

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

African (AFR) AF: 0.274 AC: 11333 AN: 41436

American (AMR) AF: 0.416 AC: 6350 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3468

East Asian (EAS) AF: 0.357 AC: 1846 AN: 5174

South Asian (SAS) AF: 0.536 AC: 2578 AN: 4810

European-Finnish (FIN) AF: 0.348 AC: 3663 AN: 10540

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.366 AC: 24896 AN: 67952

Other (OTH) AF: 0.363 AC: 769 AN: 2116

Alfa AF: 0.226 Hom.: 559

Bravo AF: 0.347

Asia WGS AF: 0.385 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.65
DANN	Benign	0.53
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11204722; hg19: chr1-150730184; COSMIC: COSV107454259;