Genetic Variant NM_025099.6:c.3591C>G (chr17-8228243-G-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_025099.6(CTC1):c.3591C>G(p.Ser1197Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,614,090 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S1197S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0096 ( 31 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 29 hom. )

Consequence

CTC1
NM_025099.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.383

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

dyskeratosis congenita
Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
cerebroretinal microangiopathy with calcifications and cysts 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Coats plus syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CTC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-8228243-G-C is Benign according to our data. Variant chr17-8228243-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 326063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.383 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00957 (1456/152220) while in subpopulation AFR AF = 0.0332 (1381/41536). AF 95% confidence interval is 0.0318. There are 31 homozygotes in GnomAd4. There are 699 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 31 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025099.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTC1	NM_025099.6	MANE Select	c.3591C>G	p.Ser1197Ser	synonymous	Exon 23 of 23	NP_079375.3
CTC1	NM_001411067.1		c.3360C>G	p.Ser1120Ser	synonymous	Exon 21 of 21	NP_001397996.1	J3KSZ1
CTC1	NR_046431.2		n.3441C>G		non_coding_transcript_exon	Exon 22 of 22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTC1	ENST00000651323.1	MANE Select	c.3591C>G	p.Ser1197Ser	synonymous	Exon 23 of 23	ENSP00000498499.1	Q2NKJ3-1
CTC1	ENST00000932859.1		c.3558C>G	p.Ser1186Ser	synonymous	Exon 23 of 23	ENSP00000602918.1
CTC1	ENST00000968384.1		c.3495C>G	p.Ser1165Ser	synonymous	Exon 23 of 23	ENSP00000638443.1

Frequencies

GnomAD3 genomes

AF:

0.00955

AC:

1453

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0333

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00219

AC:

546

AN:

249530

AF XY:

0.00165

show subpopulations

Gnomad AFR exome

AF:

0.0322

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000975

AC:

1426

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000836

AC XY:

608

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0368

AC:

1233

AN:

33480

American (AMR)

AF:

0.00143

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1111996

Other (OTH)

AF:

0.00159

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00957

AC:

1456

AN:

152220

Hom.:

Cov.:

AF XY:

0.00939

AC XY:

699

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0332

AC:

1381

AN:

41536

American (AMR)

AF:

0.00327

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67996

Other (OTH)

AF:

0.00992

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

136

204

272

340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cerebroretinal microangiopathy with calcifications and cysts 1 (2)

Dyskeratosis congenita (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.2

(source)

DANN

Benign

0.53

PhyloP100

-0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over