rs1415148

Variant names:

• chr1-150733279-G-A
• rs1415148
• NM_004079.5:c.897-134C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-150733279-G-A
• chr1-150733279-G-C
• chr1-150733279-G-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.897-134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 604,912 control chromosomes in the GnomAD database, including 51,143 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 (11592 hom., cov: 32)
  • Exomes 𝑓: 0.41 (39551 hom.)
• Consequence: CTSS NM_004079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSS	NM_004079.5	c.897-134C>T		intron_variant	Intron 7 of 7	ENST00000368985.8	NP_004070.3
CTSS	NM_001199739.2	c.747-134C>T		intron_variant	Intron 6 of 6		NP_001186668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSS	ENST00000368985.8	c.897-134C>T		intron_variant	Intron 7 of 7	1	NM_004079.5	ENSP00000357981.3

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58541 AN: 151844 Hom.: 11582 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.412 AC: 186840 AN: 452950 Hom.: 39551 AF XY: 0.419 AC XY: 100389 AN XY: 239606

African (AFR) AF: 0.313 AC: 3787 AN: 12100

American (AMR) AF: 0.421 AC: 7309 AN: 17344

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 6200 AN: 12674

East Asian (EAS) AF: 0.369 AC: 10406 AN: 28236

South Asian (SAS) AF: 0.536 AC: 23008 AN: 42924

European-Finnish (FIN) AF: 0.402 AC: 11624 AN: 28936

Middle Eastern (MID) AF: 0.436 AC: 1391 AN: 3192

European-Non Finnish (NFE) AF: 0.399 AC: 112815 AN: 282462

Other (OTH) AF: 0.411 AC: 10300 AN: 25082

GnomAD4 genome AF: 0.385 AC: 58569 AN: 151962 Hom.: 11592 Cov.: 32 AF XY: 0.390 AC XY: 28965 AN XY: 74294

African (AFR) AF: 0.309 AC: 12785 AN: 41426

American (AMR) AF: 0.435 AC: 6647 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1709 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1849 AN: 5176

South Asian (SAS) AF: 0.549 AC: 2645 AN: 4818

European-Finnish (FIN) AF: 0.402 AC: 4235 AN: 10544

Middle Eastern (MID) AF: 0.421 AC: 122 AN: 290

European-Non Finnish (NFE) AF: 0.405 AC: 27497 AN: 67944

Other (OTH) AF: 0.398 AC: 839 AN: 2110

Alfa AF: 0.370 Hom.: 4277

Bravo AF: 0.377

Asia WGS AF: 0.391 AC: 1360 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.5
DANN	Benign	0.37
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: rs1415148; hg19: chr1-150705755; COSMIC: COSV107454258; COSMIC: COSV107454258;