rs688858

Positions:

• chr11-88280095-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000678554.1(CTSC):​c.*86+10307C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 151,998 control chromosomes in the GnomAD database, including 38,159 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 0.71 (38159 hom., cov: 31)
• Consequence: CTSC ENST00000678554.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTSC	ENST00000678554.1	c.*86+10307C>T		intron_variant, NMD_transcript_variant				ENSP00000504541

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107255 AN: 151880 Hom.: 38122 Cov.: 31

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.706 AC: 107348 AN: 151998 Hom.: 38159 Cov.: 31 AF XY: 0.705 AC XY: 52386 AN XY: 74284

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.689

Alfa AF: 0.671 Hom.: 44969

Bravo AF: 0.711

Asia WGS AF: 0.686 AC: 2381 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.016
DANN	Benign	0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs688858; hg19: chr11-88013263;