11-88291569-TGAAAGAAAGAAAGAAAGAAAGAAA-TGAAAGAAAGAAAGAAAGAAAGAAAGAAAGAAA

Variant names:

• chr11-88291569-T-TGAAAGAAA
• rs36141641
• ENST00000678554.1:n.890-1063_890-1062insTTTCTTTC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000678554.1(CTSC):​n.890-1063_890-1062insTTTCTTTC 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 0.019 (66 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0193 (2440/126424) while in subpopulation AFR AF= 0.0268 (824/30734). AF 95% confidence interval is 0.0253. There are 66 homozygotes in gnomad4. There are 1159 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 66 AR gene

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_890-1062insTTTCTTTC		intron_variant	Intron 6 of 7			ENSP00000504541.1

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2439 AN: 126340 Hom.: 66 Cov.: 0

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00698

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.0111

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0293

Gnomad MID AF: 0.00357

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0190

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

GnomAD4 genome AF: 0.0193 AC: 2440 AN: 126424 Hom.: 66 Cov.: 0 AF XY: 0.0192 AC XY: 1159 AN XY: 60274

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.0113

Gnomad4 EAS AF: 0.0109

Gnomad4 SAS AF: 0.0132

Gnomad4 FIN AF: 0.0293

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.0189

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;