Variant 17-3636748-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000381870.8(CTNS):c.-230+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 153,334 control chromosomes in the GnomAD database, including 1,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1851 hom., cov: 34)

Exomes 𝑓: 0.14 ( 15 hom. )

Consequence

CTNS
ENST00000381870.8 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.54

Variant links:

Genes affected

CTNS (HGNC:2518): (cystinosin, lysosomal cystine transporter) This gene encodes a seven-transmembrane domain protein that functions to transport cystine out of lysosomes. Its activity is driven by the H+ electrochemical gradient of the lysosomal membrane. Mutations in this gene cause cystinosis, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

CTNS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 17-3636748-G-A is Benign according to our data. Variant chr17-3636748-G-A is described in ClinVar as [Benign]. Clinvar id is 322822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNS	NM_004937.3 linkuse as main transcript			upstream_gene_variant		ENST00000046640.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNS	ENST00000046640.9 linkuse as main transcript			upstream_gene_variant		1	NM_004937.3	P1	O60931-1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20993

AN:

152166

Hom.:

1845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0386

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.152

GnomAD4 exome

AF:

0.140

AC:

147

AN:

1050

Hom.:

Cov.:

AF XY:

0.142

AC XY:

102

AN XY:

716

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.100

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.231

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.138

AC:

21012

AN:

152284

Hom.:

1851

Cov.:

AF XY:

0.142

AC XY:

10552

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0385

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.210

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.156

Alfa

AF:

0.158

Hom.:

796

Bravo

AF:

0.133

Asia WGS

AF:

0.227

AC:

787

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ocular cystinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Nephropathic cystinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

Cadd

Benign

2.2

Dann

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over