17-3660045-C-T

Variant names:

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+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,483,220 control chromosomes in the GnomAD database, including 136,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10596 hom., cov: 33)

Exomes 𝑓: 0.43 ( 125862 hom. )

Consequence

CTNS
NM_004937.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.489

Publications

7 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: Myriad Women’s Health
nephropathic cystinosis
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, G2P
juvenile nephropathic cystinosis
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
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=-0.82).

BP6

Variant 17-3660045-C-T is Benign according to our data. Variant chr17-3660045-C-T is described in ClinVar as Benign. ClinVar VariationId is 1184687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 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
CTNS	NM_004937.3	MANE Select	c.970+70C>T	intron	N/A	NP_004928.2
CTNS	NM_001031681.3		c.970+70C>T	intron	N/A	NP_001026851.2
CTNS	NM_001374492.1		c.970+70C>T	intron	N/A	NP_001361421.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CTNS	ENST00000046640.9	TSL:1 MANE Select	c.970+70C>T	intron	N/A	ENSP00000046640.4
CTNS	ENST00000381870.8	TSL:1	c.970+70C>T	intron	N/A	ENSP00000371294.3
CTNS	ENST00000673965.1		c.970+70C>T	intron	N/A	ENSP00000500995.1

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52608

AN:

152010

Hom.:

10601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.379

GnomAD4 exome

AF:

0.427

AC:

567767

AN:

1331092

Hom.:

125862

Cov.:

AF XY:

0.425

AC XY:

283719

AN XY:

668012

show subpopulations

African (AFR)

AF:

0.131

AC:

4043

AN:

30894

American (AMR)

AF:

0.347

AC:

15382

AN:

44286

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

9722

AN:

25126

East Asian (EAS)

AF:

0.213

AC:

8329

AN:

39028

South Asian (SAS)

AF:

0.327

AC:

27271

AN:

83418

European-Finnish (FIN)

AF:

0.468

AC:

24108

AN:

51560

Middle Eastern (MID)

AF:

0.364

AC:

1445

AN:

3974

European-Non Finnish (NFE)

AF:

0.457

AC:

455744

AN:

997086

Other (OTH)

AF:

0.390

AC:

21723

AN:

55720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

17119

34239

51358

68478

85597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12816

25632

38448

51264

64080

<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:

0.346

AC:

52601

AN:

152128

Hom.:

10596

Cov.:

AF XY:

0.345

AC XY:

25649

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.148

AC:

6142

AN:

41542

American (AMR)

AF:

0.369

AC:

5640

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

1331

AN:

3468

East Asian (EAS)

AF:

0.180

AC:

929

AN:

5156

South Asian (SAS)

AF:

0.321

AC:

1547

AN:

4826

European-Finnish (FIN)

AF:

0.472

AC:

5000

AN:

10596

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30768

AN:

67928

Other (OTH)

AF:

0.373

AC:

789

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1660

3319

4979

6638

8298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.393

Hom.:

1572

Bravo

AF:

0.329

Asia WGS

AF:

0.238

AC:

831

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 28, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nephropathic cystinosis

Benign:2

Sep 04, 2023

Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

ClinVar: Benign

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ocular cystinosis

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.4

(source)

DANN

Benign

0.53

PhyloP100

-0.49

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over