Variant rs222753 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+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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNS	NM_004937.3 linkuse as main transcript	c.970+70C>T		intron_variant		ENST00000046640.9	NP_004928.2	O60931-1A0A0S2Z3K3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNS	ENST00000046640.9 linkuse as main transcript	c.970+70C>T		intron_variant		1	NM_004937.3	ENSP00000046640.4		O60931-1

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

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.213

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.468

Gnomad4 NFE exome

AF:

0.457

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.346

AC:

52601

AN:

152128

Hom.:

10596

Cov.:

AF XY:

0.345

AC XY:

25649

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.369

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.472

Gnomad4 NFE

AF:

0.453

Gnomad4 OTH

AF:

0.373

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 28, 2018	- -

Nephropathic cystinosis

Benign:2

Benign, criteria provided, single submitter	research	Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences	Sep 04, 2023	ClinVar: Benign -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Ocular cystinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.4

DANN

Benign

0.53

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