rs111977802

Variant names:

• chr17-3636541-T-C
• rs111977802
• ENST00000381870.8:c.-397T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-3636541-T-C
• chr17-3636541-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001031681.3(CTNS):​c.-397T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 320,972 control chromosomes in the GnomAD database, including 770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (290 hom., cov: 33)
  • Exomes 𝑓: 0.068 (480 hom.)
• Consequence: CTNS NM_001031681.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.521
• Publications: 3 publications found

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: ClinGen, Myriad Women’s Health
• nephropathic cystinosis

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics
• juvenile nephropathic cystinosis

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• ocular cystinosis

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• nephropathic infantile cystinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 17-3636541-T-C is Benign according to our data. Variant chr17-3636541-T-C is described in ClinVar as Benign. ClinVar VariationId is 322815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031681.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNS	NM_001031681.3		c.-397T>C		5_prime_UTR	Exon 1 of 13	NP_001026851.2	O60931-2
	CTNS	NM_004937.3	MANE Select	c.-520T>C		upstream_gene	N/A	NP_004928.2	O60931-1
	CTNS	NM_001374492.1		c.-520T>C		upstream_gene	N/A	NP_001361421.1	O60931-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNS	ENST00000381870.8	TSL:1	c.-397T>C		5_prime_UTR	Exon 1 of 13	ENSP00000371294.3	O60931-2
	CTNS	ENST00000673965.1		c.-392T>C		5_prime_UTR	Exon 1 of 12	ENSP00000500995.1	O60931-1
	CTNS	ENST00000901058.1		c.-397T>C		5_prime_UTR	Exon 1 of 12	ENSP00000571117.1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9222 AN: 151610 Hom.: 286 Cov.: 33

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0927

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0819

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.0572

GnomAD4 exome AF: 0.0677 AC: 11452 AN: 169244 Hom.: 480 Cov.: 0 AF XY: 0.0687 AC XY: 5974 AN XY: 87018

African (AFR) AF: 0.0440 AC: 205 AN: 4662

American (AMR) AF: 0.0498 AC: 221 AN: 4436

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 619 AN: 6166

East Asian (EAS) AF: 0.000316 AC: 4 AN: 12648

South Asian (SAS) AF: 0.0849 AC: 1006 AN: 11852

European-Finnish (FIN) AF: 0.0628 AC: 795 AN: 12668

Middle Eastern (MID) AF: 0.102 AC: 88 AN: 862

European-Non Finnish (NFE) AF: 0.0738 AC: 7746 AN: 104936

Other (OTH) AF: 0.0697 AC: 768 AN: 11014

GnomAD4 genome AF: 0.0609 AC: 9246 AN: 151728 Hom.: 290 Cov.: 33 AF XY: 0.0601 AC XY: 4454 AN XY: 74126

African (AFR) AF: 0.0446 AC: 1842 AN: 41344

American (AMR) AF: 0.0492 AC: 752 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0927 AC: 321 AN: 3464

East Asian (EAS) AF: 0.00175 AC: 9 AN: 5146

South Asian (SAS) AF: 0.0826 AC: 397 AN: 4804

European-Finnish (FIN) AF: 0.0649 AC: 684 AN: 10536

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4960 AN: 67848

Other (OTH) AF: 0.0618 AC: 130 AN: 2102

Alfa AF: 0.0615 Hom.: 47

Bravo AF: 0.0579

Asia WGS AF: 0.0360 AC: 127 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Nephropathic cystinosis (1)
-	-	1	Ocular cystinosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.7
DANN	Benign	0.52
PhyloP100		-0.52
PromoterAI		0.0094	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs111977802; hg19: chr17-3539835;