Variant 11-88335088-GAAA-GAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001814.6(CTSC):c.173-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,133,870 control chromosomes in the GnomAD database, including 593 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 376 hom., cov: 29)

Exomes 𝑓: 0.12 ( 217 hom. )

Consequence

CTSC
NM_001814.6 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.410

Variant links:

Genes affected

CTSC (HGNC:2528): (cathepsin C) This gene encodes a member of the peptidase C1 family and lysosomal cysteine proteinase that appears to be a central coordinator for activation of many serine proteinases in cells of the immune system. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate heavy and light chains that form a disulfide-linked dimer. A portion of the propeptide acts as an intramolecular chaperone for the folding and stabilization of the mature enzyme. This enzyme requires chloride ions for activity and can degrade glucagon. Defects in the encoded protein have been shown to be a cause of Papillon-Lefevre syndrome, an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis. [provided by RefSeq, Nov 2015]

CTSC links:

CTSC (HGNC:):

CTSC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-88335088-GA-G is Benign according to our data. Variant chr11-88335088-GA-G is described in ClinVar as [Benign]. Clinvar id is 402573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-88335088-GA-G is described in Lovd as [Benign]. Variant chr11-88335088-GA-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CTSC	NM_001814.6 linkuse as main transcript	c.173-7delT	splice_region_variant, intron_variant	ENST00000227266.10	NP_001805.4	P53634-1
CTSC	NM_001114173.3 linkuse as main transcript	c.173-7delT	splice_region_variant, intron_variant		NP_001107645.1	P53634-3
CTSC	NM_148170.5 linkuse as main transcript	c.173-7delT	splice_region_variant, intron_variant		NP_680475.1	P53634-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSC	ENST00000227266.10 linkuse as main transcript	c.173-7delT		splice_region_variant, intron_variant		1	NM_001814.6	ENSP00000227266.4		P53634-1

Frequencies

GnomAD3 genomes

AF:

0.0892

AC:

9633

AN:

107956

Hom.:

374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.0387

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.00886

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.0867

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0417

Gnomad NFE

AF:

0.0589

Gnomad OTH

AF:

0.0774

GnomAD4 exome

AF:

0.118

AC:

120938

AN:

1025878

Hom.:

217

Cov.:

AF XY:

0.116

AC XY:

59814

AN XY:

515860

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.154

Gnomad4 ASJ exome

AF:

0.0739

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.0894

AC:

9652

AN:

107992

Hom.:

376

Cov.:

AF XY:

0.0931

AC XY:

4845

AN XY:

52016

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.102

Gnomad4 ASJ

AF:

0.00886

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.0870

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.0589

Gnomad4 OTH

AF:

0.0792

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Papillon-Lefèvre syndrome;C1855627:Haim-Munk syndrome;C4551681:Periodontitis, aggressive 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over