dbSNP rs201146538: CTC1:p.His726His (chr17-8232110-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_025099.6(CTC1):c.2178C>T(p.His726His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CTC1
NM_025099.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.322

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):

cerebroretinal microangiopathy with calcifications and cysts 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
dyskeratosis congenita
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-8232110-G-A is Benign according to our data. Variant chr17-8232110-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 529194.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.322 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTC1	NM_025099.6 link	c.2178C>T	p.His726His	synonymous_variant	Exon 13 of 23	ENST00000651323.1	NP_079375.3	Q2NKJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTC1	ENST00000651323.1 link	c.2178C>T	p.His726His	synonymous_variant	Exon 13 of 23		NM_025099.6	ENSP00000498499.1		Q2NKJ3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.21e-7

AC:

AN:

1386716

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683672

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30650

American (AMR)

AF:

0.00

AC:

AN:

31050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20550

East Asian (EAS)

AF:

0.00

AC:

AN:

39192

South Asian (SAS)

AF:

0.00

AC:

AN:

72388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50240

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5362

European-Non Finnish (NFE)

AF:

9.26e-7

AC:

AN:

1080194

Other (OTH)

AF:

0.00

AC:

AN:

57090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dyskeratosis congenita

Benign:1

Aug 01, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.29

(source)

DANN

Benign

0.33

PhyloP100

-0.32

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over