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1-150747785-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004079.5(CTSS):c.888G>T(p.Val296=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0088 in 1,606,942 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 8 hom., cov: 31)
Exomes 𝑓: 0.0091 ( 88 hom. )

Consequence

CTSS
NM_004079.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.455
Variant links:
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 -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-150747785-C-A is Benign according to our data. Variant chr1-150747785-C-A is described in ClinVar as [Benign]. Clinvar id is 777937.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.455 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CTSSNM_004079.5 linkuse as main transcriptc.888G>T p.Val296= synonymous_variant 7/8 ENST00000368985.8
CTSSNM_001199739.2 linkuse as main transcriptc.738G>T p.Val246= synonymous_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTSSENST00000368985.8 linkuse as main transcriptc.888G>T p.Val296= synonymous_variant 7/81 NM_004079.5 P1P25774-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00625
AC:
950
AN:
152056
Hom.:
8
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00159
Gnomad AMI
AF:
0.0164
Gnomad AMR
AF:
0.00144
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0120
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0104
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00641
AC:
1602
AN:
250050
Hom.:
12
AF XY:
0.00636
AC XY:
859
AN XY:
135152
show subpopulations
Gnomad AFR exome
AF:
0.00160
Gnomad AMR exome
AF:
0.000703
Gnomad ASJ exome
AF:
0.00159
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0124
Gnomad NFE exome
AF:
0.0109
Gnomad OTH exome
AF:
0.00541
GnomAD4 exome
AF:
0.00907
AC:
13188
AN:
1454768
Hom.:
88
Cov.:
28
AF XY:
0.00878
AC XY:
6357
AN XY:
724186
show subpopulations
Gnomad4 AFR exome
AF:
0.00135
Gnomad4 AMR exome
AF:
0.000633
Gnomad4 ASJ exome
AF:
0.00134
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000350
Gnomad4 FIN exome
AF:
0.0128
Gnomad4 NFE exome
AF:
0.0109
Gnomad4 OTH exome
AF:
0.00607
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00624
AC:
950
AN:
152174
Hom.:
8
Cov.:
31
AF XY:
0.00668
AC XY:
497
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.00159
Gnomad4 AMR
AF:
0.00144
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0120
Gnomad4 NFE
AF:
0.0104
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00712
Hom.:
2
Bravo
AF:
0.00544
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00894
EpiControl
AF:
0.00836

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 07, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
Cadd
Benign
9.9
Dann
Benign
0.77

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140408537; hg19: chr1-150720261; API