17-8235109-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_025099.6(CTC1):​c.1383G>A​(p.Gln461=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,614,190 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 9 hom., cov: 32)
Exomes 𝑓: 0.016 ( 230 hom. )

Consequence

CTC1
NM_025099.6 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.34
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 17-8235109-C-T is Benign according to our data. Variant chr17-8235109-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 128859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.34 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.011 (1673/152334) while in subpopulation NFE AF= 0.0194 (1317/68022). AF 95% confidence interval is 0.0185. There are 9 homozygotes in gnomad4. There are 789 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CTC1NM_025099.6 linkuse as main transcriptc.1383G>A p.Gln461= synonymous_variant 8/23 ENST00000651323.1 NP_079375.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CTC1ENST00000651323.1 linkuse as main transcriptc.1383G>A p.Gln461= synonymous_variant 8/23 NM_025099.6 ENSP00000498499 P1Q2NKJ3-1

Frequencies

GnomAD3 genomes
AF:
0.0110
AC:
1673
AN:
152216
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00301
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00354
Gnomad ASJ
AF:
0.0121
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.00969
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0194
Gnomad OTH
AF:
0.00956
GnomAD3 exomes
AF:
0.0105
AC:
2618
AN:
249392
Hom.:
30
AF XY:
0.0104
AC XY:
1408
AN XY:
135358
show subpopulations
Gnomad AFR exome
AF:
0.00239
Gnomad AMR exome
AF:
0.00319
Gnomad ASJ exome
AF:
0.0129
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00297
Gnomad FIN exome
AF:
0.00975
Gnomad NFE exome
AF:
0.0174
Gnomad OTH exome
AF:
0.0111
GnomAD4 exome
AF:
0.0160
AC:
23440
AN:
1461856
Hom.:
230
Cov.:
33
AF XY:
0.0157
AC XY:
11417
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00233
Gnomad4 AMR exome
AF:
0.00371
Gnomad4 ASJ exome
AF:
0.0128
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00312
Gnomad4 FIN exome
AF:
0.00908
Gnomad4 NFE exome
AF:
0.0191
Gnomad4 OTH exome
AF:
0.0151
GnomAD4 genome
AF:
0.0110
AC:
1673
AN:
152334
Hom.:
9
Cov.:
32
AF XY:
0.0106
AC XY:
789
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00301
Gnomad4 AMR
AF:
0.00353
Gnomad4 ASJ
AF:
0.0121
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.00969
Gnomad4 NFE
AF:
0.0194
Gnomad4 OTH
AF:
0.00946
Alfa
AF:
0.0164
Hom.:
11
Bravo
AF:
0.00979
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.0154
EpiControl
AF:
0.0155

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, no assertion criteria providedclinical testingLaboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)-- -
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxSep 23, 2020- -
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, Amsterdam University Medical Center-- -
Dyskeratosis congenita Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Cerebroretinal microangiopathy with calcifications and cysts 1 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 15, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
5.8
DANN
Benign
0.68

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.

Other links and lift over

dbSNP: rs145192682; hg19: chr17-8138427; API