rs200658590
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_025099.6(CTC1):c.477G>T(p.Leu159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,611,894 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0023 ( 6 hom., cov: 31)
Exomes 𝑓: 0.0020 ( 39 hom. )
Consequence
CTC1
NM_025099.6 synonymous
NM_025099.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.673
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
Variant 17-8238201-C-A is Benign according to our data. Variant chr17-8238201-C-A is described in ClinVar as [Benign]. Clinvar id is 210796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8238201-C-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.673 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00233 (355/152312) while in subpopulation SAS AF= 0.03 (145/4828). AF 95% confidence interval is 0.0261. There are 6 homozygotes in gnomad4. There are 199 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTC1 | NM_025099.6 | c.477G>T | p.Leu159= | synonymous_variant | 4/23 | ENST00000651323.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTC1 | ENST00000651323.1 | c.477G>T | p.Leu159= | synonymous_variant | 4/23 | NM_025099.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00228 AC: 347AN: 152194Hom.: 6 Cov.: 31
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GnomAD3 exomes AF: 0.00415 AC: 1030AN: 248364Hom.: 12 AF XY: 0.00518 AC XY: 699AN XY: 134850
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GnomAD4 exome AF: 0.00200 AC: 2915AN: 1459582Hom.: 39 Cov.: 31 AF XY: 0.00273 AC XY: 1980AN XY: 725760
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GnomAD4 genome ? AF: 0.00233 AC: 355AN: 152312Hom.: 6 Cov.: 31 AF XY: 0.00267 AC XY: 199AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dyskeratosis congenita Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
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. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 18, 2018 | - - |
Cerebroretinal microangiopathy with calcifications and cysts 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
CTC1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 14, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at