dbSNP rs3027247: CTC1:c.*631T>G (chr17-8227549-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_025099.6(CTC1):c.*631T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,166 control chromosomes in the GnomAD database, including 5,942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5921 hom., cov: 31)

Exomes 𝑓: 0.24 ( 21 hom. )

Consequence

CTC1
NM_025099.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.271

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-8227549-A-C is Benign according to our data. Variant chr17-8227549-A-C is described in ClinVar as [Benign]. Clinvar id is 326051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTC1	NM_025099.6 link	c.*631T>G		3_prime_UTR_variant	Exon 23 of 23	ENST00000651323.1	NP_079375.3	Q2NKJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTC1	ENST00000651323 link	c.*631T>G		3_prime_UTR_variant	Exon 23 of 23		NM_025099.6	ENSP00000498499.1		Q2NKJ3-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40876

AN:

151570

Hom.:

5913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.266

GnomAD4 exome

AF:

0.241

AC:

115

AN:

478

Hom.:

Cov.:

AF XY:

0.254

AC XY:

AN XY:

276

show subpopulations

Gnomad4 AMR exome

AF:

0.269

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.0556

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.242

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.270

AC:

40921

AN:

151688

Hom.:

5921

Cov.:

AF XY:

0.269

AC XY:

19941

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.415

Gnomad4 ASJ

AF:

0.338

Gnomad4 EAS

AF:

0.344

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.223

Gnomad4 NFE

AF:

0.283

Gnomad4 OTH

AF:

0.269

Alfa

AF:

0.291

Hom.:

13817

Bravo

AF:

0.284

Asia WGS

AF:

0.279

AC:

969

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dyskeratosis congenita

Benign:1

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

-0.85

CADD

Benign

0.67

DANN

Benign

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