rs437287

chr17-3654205-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004937.3(CTNS):c.226-793C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,120 control chromosomes in the GnomAD database, including 4,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4823 hom., cov: 33)
• Consequence: CTNS NM_004937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600

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]

LOC105371493 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNS	NM_004937.3	c.226-793C>T		intron_variant		ENST00000046640.9
LOC105371493	XR_007065579.1	n.799G>A		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNS	ENST00000046640.9	c.226-793C>T		intron_variant		1	NM_004937.3	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34791 AN: 152002 Hom.: 4826 Cov.: 33

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.229 AC: 34792 AN: 152120 Hom.: 4823 Cov.: 33 AF XY: 0.232 AC XY: 17288 AN XY: 74366

Gnomad4 AFR AF: 0.0853

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.239

Alfa AF: 0.241 Hom.: 600

Bravo AF: 0.228

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.9
Dann	Benign	0.75

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: rs437287; hg19: chr17-3557499;