11-88291569-TGAAAGAAAGAAAGAAAGAAAGAAA-TGAAAGAAAGAAAGAAAGAAA

Variant names:

• chr11-88291569-TGAAA-T
• rs36141641
• ENST00000678554.1:n.890-1066_890-1063delTTTC

Variant summary

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

The ENST00000678554.1(CTSC):​n.890-1066_890-1063delTTTC 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 0.026 (65 hom., cov: 0)
• Consequence: CTSC ENST00000678554.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 eas. gnomad4 allele frequency = 0.026 (3283/126428) while in subpopulation EAS AF= 0.047 (207/4404). AF 95% confidence interval is 0.0418. There are 65 homozygotes in gnomad4. There are 1671 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 65 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.890-1066_890-1063delTTTC		intron_variant	Intron 6 of 7			ENSP00000504541.1

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3276 AN: 126344 Hom.: 65 Cov.: 0

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0663

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.0204

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.00714

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0218

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

GnomAD4 genome AF: 0.0260 AC: 3283 AN: 126428 Hom.: 65 Cov.: 0 AF XY: 0.0277 AC XY: 1671 AN XY: 60282

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.0470

Gnomad4 SAS AF: 0.0210

Gnomad4 FIN AF: 0.0577

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0217

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;