rs222753

chr17-3660045-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.489

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]

ACMG classification

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	UniProt
CTNS	NM_004937.3	c.970+70C>T		intron_variant		ENST00000046640.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNS	ENST00000046640.9	c.970+70C>T		intron_variant		1	NM_004937.3	P1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52608 AN: 152010 Hom.: 10601 Cov.: 33

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.: 20 AF XY: 0.425 AC XY: 283719 AN XY: 668012

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.: 33 AF XY: 0.345 AC XY: 25649 AN XY: 74384

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 28, 2018

- -

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

Other links and lift over

dbSNP: rs222753; hg19: chr17-3563339; COSMIC: COSV50440606; COSMIC: COSV50440606;