rs688858

Variant names:

• chr11-88280095-G-A
• rs688858
• ENST00000678554.1:n.*86+10307C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000678554.1(CTSC):​n.*86+10307C>T variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• Papillon-Lefevre disease

  Inheritance: AR, Unknown Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• Haim-Munk syndrome

  Inheritance: Unknown, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
• ectodermal dysplasia syndrome

  Inheritance: AR Classification: STRONG Submitted by: Illumina
• periodontitis, aggressive 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000678554.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTSC	ENST00000678554.1		n.*86+10307C>T		intron	N/A	ENSP00000504541.1

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

African (AFR) AF: 0.786 AC: 32592 AN: 41482

American (AMR) AF: 0.697 AC: 10632 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2372 AN: 3468

East Asian (EAS) AF: 0.710 AC: 3659 AN: 5150

South Asian (SAS) AF: 0.657 AC: 3159 AN: 4808

European-Finnish (FIN) AF: 0.688 AC: 7276 AN: 10574

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.668 AC: 45368 AN: 67950

Other (OTH) AF: 0.689 AC: 1455 AN: 2112

Alfa AF: 0.676 Hom.: 58188

Bravo AF: 0.711

Asia WGS AF: 0.686 AC: 2381 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.016
DANN	Benign	0.13
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs688858; hg19: chr11-88013263;