chr11-88291569-TGAAAGAAAGAAA-T

Variant names:

• chr11-88291569-TGAAAGAAAGAAA-T
• rs36141641
• ENST00000678554.1:n.890-1074_890-1063delTTTCTTTCTTTC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000678554.1(CTSC):​n.890-1074_890-1063delTTTCTTTCTTTC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00088 (2 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

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000878 (111/126458) while in subpopulation EAS AF = 0.00272 (12/4406). AF 95% confidence interval is 0.00157. There are 2 homozygotes in GnomAd4. There are 39 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.890-1074_890-1063delTTTCTTTCTTTC		intron_variant	Intron 6 of 7			ENSP00000504541.1

Frequencies

GnomAD3 genomes AF: 0.000870 AC: 110 AN: 126374 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.000489

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00249

Gnomad SAS AF: 0.000862

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.00168

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

GnomAD4 genome AF: 0.000878 AC: 111 AN: 126458 Hom.: 2 Cov.: 0 AF XY: 0.000647 AC XY: 39 AN XY: 60288

African (AFR) AF: 0.000488 AC: 15 AN: 30744

American (AMR) AF: 0.000786 AC: 10 AN: 12718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3192

East Asian (EAS) AF: 0.00272 AC: 12 AN: 4406

South Asian (SAS) AF: 0.000861 AC: 3 AN: 3484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.00110 AC: 68 AN: 61644

Other (OTH) AF: 0.00167 AC: 3 AN: 1800

Alfa AF: 0.00 Hom.: 223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Publications

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Other links and lift over

dbSNP: rs36141641; hg19: chr11-88024737;