rs3027235

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_025099.6(CTC1):c.2160C>T(p.Thr720Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,528,728 control chromosomes in the GnomAD database, including 665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 221 hom., cov: 32)

Exomes 𝑓: 0.018 ( 444 hom. )

Consequence

CTC1
NM_025099.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.764

Publications

4 publications found

Variant links:

Genes affected

CTC1 (HGNC:26169): (CST telomere replication complex component 1) This gene encodes a component of the CST complex. This complex plays an essential role in protecting telomeres from degradation. This protein also forms a heterodimer with the CST complex subunit STN1 to form the enzyme alpha accessory factor. This enzyme regulates DNA replication. Mutations in this gene are the cause of cerebroretinal microangiopathy with calcifications and cysts. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Mar 2012]

CTC1 Gene-Disease associations (from GenCC):

cerebroretinal microangiopathy with calcifications and cysts 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
dyskeratosis congenita
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
Coats plus syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CTC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-8232128-G-A is Benign according to our data. Variant chr17-8232128-G-A is described in ClinVar as [Benign]. Clinvar id is 326074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.764 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTC1	NM_025099.6 link	c.2160C>T	p.Thr720Thr	synonymous_variant	Exon 13 of 23	ENST00000651323.1	NP_079375.3	Q2NKJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTC1	ENST00000651323.1 link	c.2160C>T	p.Thr720Thr	synonymous_variant	Exon 13 of 23		NM_025099.6	ENSP00000498499.1		Q2NKJ3-1

Frequencies

GnomAD3 genomes

AF:

0.0388

AC:

5901

AN:

152152

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0932

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0306

GnomAD2 exomes

AF:

0.0301

AC:

4983

AN:

165530

AF XY:

0.0266

show subpopulations

Gnomad AFR exome

AF:

0.0755

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.0393

Gnomad EAS exome

AF:

0.00831

Gnomad FIN exome

AF:

0.00563

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.0253

GnomAD4 exome

AF:

0.0177

AC:

24301

AN:

1376458

Hom.:

444

Cov.:

AF XY:

0.0171

AC XY:

11615

AN XY:

677292

show subpopulations

African (AFR)

AF:

0.0772

AC:

2346

AN:

30378

American (AMR)

AF:

0.108

AC:

3151

AN:

29156

Ashkenazi Jewish (ASJ)

AF:

0.0373

AC:

754

AN:

20206

East Asian (EAS)

AF:

0.00979

AC:

381

AN:

38924

South Asian (SAS)

AF:

0.0134

AC:

954

AN:

71172

European-Finnish (FIN)

AF:

0.00635

AC:

317

AN:

49908

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

5342

European-Non Finnish (NFE)

AF:

0.0140

AC:

15058

AN:

1074726

Other (OTH)

AF:

0.0224

AC:

1267

AN:

56646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1382

2764

4147

5529

6911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0388

AC:

5914

AN:

152270

Hom.:

221

Cov.:

AF XY:

0.0397

AC XY:

2958

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0747

AC:

3103

AN:

41534

American (AMR)

AF:

0.0932

AC:

1425

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0334

AC:

116

AN:

3470

East Asian (EAS)

AF:

0.0102

AC:

AN:

5186

South Asian (SAS)

AF:

0.0118

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00480

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0152

AC:

1033

AN:

68024

Other (OTH)

AF:

0.0346

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

269

538

806

1075

1344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0255

Hom.:

179

Bravo

AF:

0.0456

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Cerebroretinal microangiopathy with calcifications and cysts 1

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 16, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dyskeratosis congenita

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.5

(source)

DANN

Benign

0.31

PhyloP100

0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs3027235

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over