rs62620189

Positions:

chr17-8232126-C-G

Variant summary

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

The NM_025099.6(CTC1):c.2162G>C(p.Gly721Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 1,529,924 control chromosomes in the GnomAD database, including 254 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 17 hom., cov: 32)

Exomes 𝑓: 0.016 ( 237 hom. )

Consequence

CTC1
NM_025099.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.933

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:

CTC1 (HGNC:):

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=0.0045121014).

BP6

Variant 17-8232126-C-G is Benign according to our data. Variant chr17-8232126-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 241580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8232126-C-G is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTC1	NM_025099.6 linkuse as main transcript	c.2162G>C	p.Gly721Ala	missense_variant	13/23	ENST00000651323.1	NP_079375.3	Q2NKJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTC1	ENST00000651323.1 linkuse as main transcript	c.2162G>C	p.Gly721Ala	missense_variant	13/23		NM_025099.6	ENSP00000498499.1		Q2NKJ3-1

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2063

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0248

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0131

AC:

2189

AN:

166804

Hom.:

AF XY:

0.0136

AC XY:

1203

AN XY:

88468

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.00834

Gnomad ASJ exome

AF:

0.00930

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.0215

Gnomad NFE exome

AF:

0.0186

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0161

AC:

22145

AN:

1377678

Hom.:

237

Cov.:

AF XY:

0.0160

AC XY:

10868

AN XY:

677954

show subpopulations

Gnomad4 AFR exome

AF:

0.00519

Gnomad4 AMR exome

AF:

0.00947

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00484

Gnomad4 FIN exome

AF:

0.0206

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0149

GnomAD4 genome

AF:

0.0135

AC:

2060

AN:

152246

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1007

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00429

Gnomad4 AMR

AF:

0.0140

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.0248

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0147

Hom.:

Bravo

AF:

0.0122

TwinsUK

AF:

0.0189

AC:

ALSPAC

AF:

0.0184

AC:

ESP6500AA

AF:

0.00410

AC:

ESP6500EA

AF:

0.0192

AC:

159

ExAC

AF:

0.0127

AC:

1512

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 28, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dyskeratosis congenita

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Sep 15, 2016

- -

Cerebroretinal microangiopathy with calcifications and cysts 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.050

DANN

Benign

0.62

DEOGEN2

Benign

0.19

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.23

PROVEAN

Benign

0.16

REVEL

Benign

0.24

Sift

Benign

0.79

Sift4G

Benign

0.67

Polyphen

0.016

Vest4

0.026

MPC

0.14

ClinPred

0.0018

GERP RS

-2.9

Varity_R

0.034

gMVP

0.15

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