rs76153698

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

cystinosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health
nephropathic cystinosis
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics
juvenile nephropathic cystinosis
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
ocular cystinosis
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
nephropathic infantile cystinosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CTNS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 257158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004937.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTNS	NM_004937.3	MANE Select	c.970+15G>A	intron	N/A	NP_004928.2	O60931-1
CTNS	NM_001031681.3		c.970+15G>A	intron	N/A	NP_001026851.2	O60931-2
CTNS	NM_001374492.1		c.970+15G>A	intron	N/A	NP_001361421.1	O60931-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTNS	ENST00000046640.9	TSL:1 MANE Select	c.970+15G>A	intron	N/A	ENSP00000046640.4	O60931-1
CTNS	ENST00000381870.8	TSL:1	c.970+15G>A	intron	N/A	ENSP00000371294.3	O60931-2
CTNS	ENST00000673965.1		c.970+15G>A	intron	N/A	ENSP00000500995.1	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

GnomAD2 exomes

AF:

0.0201

AC:

5034

AN:

250196

AF XY:

0.0195

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 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

African (AFR)

AF:

0.0696

AC:

2306

AN:

33134

American (AMR)

AF:

0.0109

AC:

487

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

443

AN:

26026

East Asian (EAS)

AF:

0.000126

AC:

AN:

39638

South Asian (SAS)

AF:

0.0208

AC:

1785

AN:

85932

European-Finnish (FIN)

AF:

0.0303

AC:

1601

AN:

52800

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

5192

European-Non Finnish (NFE)

AF:

0.0171

AC:

18765

AN:

1097174

Other (OTH)

AF:

0.0230

AC:

1378

AN:

59798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1423

2846

4270

5693

7116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

770

1540

2310

3080

3850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0319

AC:

4857

AN:

152316

Hom.:

135

Cov.:

AF XY:

0.0317

AC XY:

2360

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0706

AC:

2934

AN:

41578

American (AMR)

AF:

0.0145

AC:

222

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.0205

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0309

AC:

328

AN:

10622

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0162

AC:

1100

AN:

68016

Other (OTH)

AF:

0.0260

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

252

503

755

1006

1258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0233

Hom.:

Bravo

AF:

0.0321

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Juvenile nephropathic cystinosis;C0950123:Inborn genetic diseases;C2931013:Ocular cystinosis (1)

Nephropathic cystinosis (1)

not specified (1)

Ocular cystinosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.027

(source)

DANN

Benign

0.89

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over