rs11722604

chr4-155943599-C-Achr4-155943599-C-T

Variant summary

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

The NM_001334.3(CTSO):c.136-335G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,008 control chromosomes in the GnomAD database, including 2,525 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 0.16 (2525 hom., cov: 32)
• Consequence: CTSO NM_001334.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

Genes affected

CTSO (HGNC:2542): (cathepsin O) The protein encoded by the gene is a cysteine proteinase and a member of the papain superfamily. This proteolytic enzyme is involved in cellular protein degradation and turnover. The recombinant form of this enzyme was shown to degrade synthetic peptides typically used as substrates for cysteine proteinases and its proteolytic activity was abolished by an inhibitor of cyteine proteinase. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTSO	NM_001334.3	c.136-335G>T		intron_variant		ENST00000433477.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTSO	ENST00000433477.4	c.136-335G>T		intron_variant		1	NM_001334.3	P2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24260 AN: 151890 Hom.: 2526 Cov.: 32

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.0876

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.160 AC: 24254 AN: 152008 Hom.: 2525 Cov.: 32 AF XY: 0.154 AC XY: 11442 AN XY: 74284

Gnomad4 AFR AF: 0.0434

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.0913

Gnomad4 SAS AF: 0.0879

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.143

Alfa AF: 0.122 Hom.: 258

Bravo AF: 0.154

Asia WGS AF: 0.0920 AC: 322 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.2
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11722604; hg19: chr4-156864751;