rs618143

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000684900.1(ENSG00000288018):​n.169+9009T>A variant causes a intron, non coding transcript 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: ENST00000684900.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

Genes affected

(HGNC:):

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 -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/exons	MANE	Protein	UniProt
LOC101929174	XR_007062834.1	n.173+9009T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000684900.1	n.169+9009T>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.720

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs618143; hg19: chr11-88080233;