11-88291569-TGAAAGAAAGAAAGAAAGAAAGAAA-TGAAAGAAAGAAAGAAAGAAAGAAAGAAA

Variant names:

• chr11-88291569-T-TGAAA
• rs36141641
• ENST00000678554.1:n.890-1063_890-1062insTTTC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000678554.1(CTSC):​n.890-1063_890-1062insTTTC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.045 (224 hom., cov: 0)
• Consequence: CTSC ENST00000678554.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSC	ENST00000678554.1	n.890-1063_890-1062insTTTC		intron_variant	Intron 6 of 7			ENSP00000504541.1

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 5682 AN: 126330 Hom.: 223 Cov.: 0

Gnomad AFR AF: 0.0336

Gnomad AMI AF: 0.0349

Gnomad AMR AF: 0.0341

Gnomad ASJ AF: 0.0430

Gnomad EAS AF: 0.00317

Gnomad SAS AF: 0.0210

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.0464

Gnomad NFE AF: 0.0589

Gnomad OTH AF: 0.0469

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

GnomAD4 genome AF: 0.0450 AC: 5688 AN: 126414 Hom.: 224 Cov.: 0 AF XY: 0.0434 AC XY: 2617 AN XY: 60264

Gnomad4 AFR AF: 0.0337

Gnomad4 AMR AF: 0.0341

Gnomad4 ASJ AF: 0.0430

Gnomad4 EAS AF: 0.00318

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0589

Gnomad4 OTH AF: 0.0467

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs36141641; hg19: chr11-88024737;