chr11-88300353-T-C

Position:

• chr11-88300353-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001814.6(CTSC):​c.757+177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,240 control chromosomes in the GnomAD database, including 59,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.88 (59597 hom., cov: 32)
• Consequence: CTSC NM_001814.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0590

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-88300353-T-C is Benign according to our data. Variant chr11-88300353-T-C is described in ClinVar as [Benign]. Clinvar id is 1287626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTSC	NM_001814.6	c.757+177A>G		intron_variant		ENST00000227266.10	NP_001805.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSC	ENST00000227266.10	c.757+177A>G		intron_variant		1	NM_001814.6	ENSP00000227266.4

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134340 AN: 152122 Hom.: 59545 Cov.: 32

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.890

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.863

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.883 AC: 134451 AN: 152240 Hom.: 59597 Cov.: 32 AF XY: 0.886 AC XY: 65950 AN XY: 74446

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.890

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.898

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.864

Alfa AF: 0.852 Hom.: 6865

Bravo AF: 0.886

Asia WGS AF: 0.969 AC: 3367 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.61

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: rs217115; hg19: chr11-88033521;