17-3639977-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004937.3(CTNS):c.-19-211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,970 control chromosomes in the GnomAD database, including 14,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (14451 hom., cov: 32)
• Consequence: CTNS NM_004937.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.157

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-3639977-A-G is Benign according to our data. Variant chr17-3639977-A-G is described in ClinVar as [Benign]. Clinvar id is 1277327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNS	NM_004937.3	c.-19-211A>G		intron_variant		ENST00000046640.9
LOC105371493	XR_007065579.1	n.2150-892T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNS	ENST00000046640.9	c.-19-211A>G		intron_variant		1	NM_004937.3	P1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64679 AN: 151850 Hom.: 14447 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.426 AC: 64713 AN: 151970 Hom.: 14451 Cov.: 32 AF XY: 0.423 AC XY: 31427 AN XY: 74296

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.441

Alfa AF: 0.407 Hom.: 2945

Bravo AF: 0.413

Asia WGS AF: 0.275 AC: 957 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.0
Dann	Benign	0.41

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: rs456253; hg19: chr17-3543271;