rs618143

Variant names:

• chr11-88347065-T-A
• rs618143
• ENST00000677106.1:c.-11-9382A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-88347065-T-A
• chr11-88347065-T-G

Variant summary

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

The ENST00000677106.1(CTSC):​c.-11-9382A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,170 control chromosomes in the GnomAD database, including 41,036 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 0.73 (41036 hom., cov: 33)
• Consequence: CTSC ENST00000677106.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 2 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)

ENSG00000288018 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101929174	NR_188508.1	n.173+9009T>A		intron_variant	Intron 1 of 5
LOC101929174	NR_188509.1	n.173+9009T>A		intron_variant	Intron 1 of 3
LOC101929174	NR_188510.1	n.173+9009T>A		intron_variant	Intron 1 of 4
LOC101929174	NR_188511.1	n.173+9009T>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSC	ENST00000677106.1	c.-11-9382A>T		intron_variant	Intron 1 of 4			ENSP00000504568.1
CTSC	ENST00000677661.1	n.-11-9382A>T		intron_variant	Intron 2 of 9			ENSP00000503323.1
ENSG00000288018	ENST00000684900.2	n.212+9009T>A		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111160 AN: 152052 Hom.: 41007 Cov.: 33

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.731 AC: 111248 AN: 152170 Hom.: 41036 Cov.: 33 AF XY: 0.734 AC XY: 54625 AN XY: 74390

African (AFR) AF: 0.835 AC: 34680 AN: 41522

American (AMR) AF: 0.742 AC: 11351 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2191 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4172 AN: 5176

South Asian (SAS) AF: 0.810 AC: 3915 AN: 4832

European-Finnish (FIN) AF: 0.694 AC: 7333 AN: 10572

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45290 AN: 67982

Other (OTH) AF: 0.720 AC: 1523 AN: 2114

Alfa AF: 0.694 Hom.: 4595

Bravo AF: 0.739

Asia WGS AF: 0.798 AC: 2774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs618143; hg19: chr11-88080233;