Variant chr17-3659990-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 NM_004937.3(CTNS):c.970+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,596,700 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 135 hom., cov: 34)

Exomes 𝑓: 0.019 ( 333 hom. )

Consequence

CTNS
NM_004937.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.27

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=-0.84).

BP6

Variant 17-3659990-G-A is Benign according to our data. Variant chr17-3659990-G-A is described in ClinVar as [Benign]. Clinvar id is 257158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-3659990-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNS	NM_004937.3 linkuse as main transcript	c.970+15G>A		intron_variant		ENST00000046640.9	NP_004928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNS	ENST00000046640.9 linkuse as main transcript	c.970+15G>A		intron_variant		1	NM_004937.3	ENSP00000046640	P1	O60931-1

Frequencies

GnomAD3 genomes

AF:

0.0319

AC:

4852

AN:

152198

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0706

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.0309

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0201

AC:

5034

AN:

250196

Hom.:

AF XY:

0.0195

AC XY:

2643

AN XY:

135520

show subpopulations

Gnomad AFR exome

AF:

0.0681

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0209

Gnomad FIN exome

AF:

0.0305

Gnomad NFE exome

AF:

0.0176

Gnomad OTH exome

AF:

0.0214

GnomAD4 exome

AF:

0.0186

AC:

26850

AN:

1444384

Hom.:

333

Cov.:

AF XY:

0.0184

AC XY:

13235

AN XY:

719412

show subpopulations

Gnomad4 AFR exome

AF:

0.0696

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0208

Gnomad4 FIN exome

AF:

0.0303

Gnomad4 NFE exome

AF:

0.0171

Gnomad4 OTH exome

AF:

0.0230

GnomAD4 genome

AF:

0.0319

AC:

4857

AN:

152316

Hom.:

135

Cov.:

AF XY:

0.0317

AC XY:

2360

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0706

Gnomad4 AMR

AF:

0.0145

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.0309

Gnomad4 NFE

AF:

0.0162

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0240

Hom.:

Bravo

AF:

0.0321

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2018	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 03, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jun 05, 2017	Variant summary: The CTNS c.970+15G>A variant involves the alteration of a non-conserved intronic nucleotide at a position not widely known to affect gene splicing. Mutation taster predicts a benign outcome for this variant. This variant was found in 2496/120078 control chromosomes (45 homozygotes) from ExAC at a frequency of 0.0207865, which is approximately 8 times the estimated maximal expected allele frequency of a pathogenic CTNS variant (0.0025), suggesting this variant is likely a benign polymorphism. It is more common in African subpopulation with an allele frequency of 6.5% (674/10238 chromosomes). This variant was found in a cystinosis patient who carried c.140+1G>T in homozygous state, further supporting benign outcome of the variant of interest. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign/benign. Taken together, this variant is classified as benign. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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. -

Nephropathic cystinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Juvenile nephropathic cystinosis;C0950123:Inborn genetic diseases;C2931013:Ocular cystinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.027

DANN

Benign

0.89

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