17-8235251-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025099.6(CTC1):c.1241G>C(p.Gly414Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,613,968 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 18 hom., cov: 32)

Exomes 𝑓: 0.016 ( 240 hom. )

Consequence

CTC1
NM_025099.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.01

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008434802).

BP6

Variant 17-8235251-C-G is Benign according to our data. Variant chr17-8235251-C-G is described in ClinVar as [Benign]. Clinvar id is 241577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8235251-C-G is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTC1	NM_025099.6 link	c.1241G>C	p.Gly414Ala	missense_variant	Exon 8 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.1241G>C	p.Gly414Ala	missense_variant	Exon 8 of 23		NM_025099.6	ENSP00000498499.1		Q2NKJ3-1

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2056

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0246

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.0129

AC:

3214

AN:

248690

Hom.:

AF XY:

0.0132

AC XY:

1782

AN XY:

135072

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.00847

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00405

Gnomad FIN exome

AF:

0.0213

Gnomad NFE exome

AF:

0.0184

Gnomad OTH exome

AF:

0.0139

GnomAD4 exome

AF:

0.0158

AC:

23050

AN:

1461664

Hom.:

240

Cov.:

AF XY:

0.0157

AC XY:

11404

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00496

Gnomad4 AMR exome

AF:

0.00932

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00480

Gnomad4 FIN exome

AF:

0.0206

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0148

GnomAD4 genome

AF:

0.0135

AC:

2053

AN:

152304

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1004

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00423

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0246

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0142

Hom.:

Bravo

AF:

0.0122

TwinsUK

AF:

0.0189

AC:

ALSPAC

AF:

0.0182

AC:

ESP6500AA

AF:

0.00463

AC:

ESP6500EA

AF:

0.0203

AC:

171

ExAC

AF:

0.0134

AC:

1620

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0196

EpiControl

AF:

0.0192

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cerebroretinal microangiopathy with calcifications and cysts 1

Benign:2

Oct 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Apr 07, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 12, 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

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0084

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.85

REVEL

Benign

0.26

Sift

Benign

0.63

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.17

MPC

0.59

ClinPred

0.034

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over