rs163801

Variant names:

• chr20-59003559-A-G
• rs163801
• NM_001336.4:c.308-1915T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-59003559-A-G
• chr20-59003559-A-T

Variant summary

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

The NM_001336.4(CTSZ):​c.308-1915T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,234 control chromosomes in the GnomAD database, including 54,047 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 0.84 (54047 hom., cov: 33)
• Consequence: CTSZ NM_001336.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.76
• Publications: 11 publications found

Genes affected

CTSZ (HGNC:2547): (cathepsin Z) The protein encoded by this gene is a lysosomal cysteine proteinase and member of the peptidase C1 family. It exhibits both carboxy-monopeptidase and carboxy-dipeptidase activities. The encoded protein has also been known as cathepsin X and cathepsin P. This gene is expressed ubiquitously in cancer cell lines and primary tumors and, like other members of this family, may be involved in tumorigenesis. [provided by RefSeq, Oct 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTSZ	NM_001336.4	c.308-1915T>C		intron_variant	Intron 2 of 5	ENST00000217131.6	NP_001327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTSZ	ENST00000217131.6	c.308-1915T>C		intron_variant	Intron 2 of 5	1	NM_001336.4	ENSP00000217131.5

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127710 AN: 152116 Hom.: 53990 Cov.: 33

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.840 AC: 127824 AN: 152234 Hom.: 54047 Cov.: 33 AF XY: 0.840 AC XY: 62527 AN XY: 74424

African (AFR) AF: 0.929 AC: 38588 AN: 41544

American (AMR) AF: 0.761 AC: 11631 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2820 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4499 AN: 5186

South Asian (SAS) AF: 0.826 AC: 3974 AN: 4814

European-Finnish (FIN) AF: 0.845 AC: 8950 AN: 10596

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54677 AN: 68014

Other (OTH) AF: 0.807 AC: 1703 AN: 2110

Alfa AF: 0.812 Hom.: 35263

Bravo AF: 0.837

Asia WGS AF: 0.823 AC: 2866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.88
DANN	Benign	0.24
PhyloP100		-4.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs163801; hg19: chr20-57578614;