Variant 17-8247860-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025099.6(CTC1):c.33+144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 747,678 control chromosomes in the GnomAD database, including 1,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 220 hom., cov: 31)

Exomes 𝑓: 0.057 ( 1270 hom. )

Consequence

CTC1
NM_025099.6 intron

Scores

Splicing: ADA: 0.00008497

Clinical Significance

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

Conservation

PhyloP100: 0.0200

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:

PFAS (HGNC:8863): (phosphoribosylformylglycinamidine synthase) Purines are necessary for many cellular processes, including DNA replication, transcription, and energy metabolism. Ten enzymatic steps are required to synthesize inosine monophosphate (IMP) in the de novo pathway of purine biosynthesis. The enzyme encoded by this gene catalyzes the fourth step of IMP biosynthesis. [provided by RefSeq, Jul 2008]

PFAS 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=-0.79).

BP6

Variant 17-8247860-G-A is Benign according to our data. Variant chr17-8247860-G-A is described in ClinVar as [Benign]. Clinvar id is 1227785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTC1	NM_025099.6 linkuse as main transcript	c.33+144C>T		intron_variant		ENST00000651323.1	NP_079375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTC1	ENST00000651323.1 linkuse as main transcript	c.33+144C>T		intron_variant			NM_025099.6	ENSP00000498499	P1	Q2NKJ3-1

Frequencies

GnomAD3 genomes

AF:

0.0465

AC:

7083

AN:

152172

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0329

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00952

Gnomad FIN

AF:

0.0937

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0710

Gnomad OTH

AF:

0.0440

GnomAD4 exome

AF:

0.0573

AC:

34105

AN:

595388

Hom.:

1270

Cov.:

AF XY:

0.0552

AC XY:

17367

AN XY:

314466

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.0262

Gnomad4 ASJ exome

AF:

0.0182

Gnomad4 EAS exome

AF:

0.0000946

Gnomad4 SAS exome

AF:

0.0126

Gnomad4 FIN exome

AF:

0.0880

Gnomad4 NFE exome

AF:

0.0726

Gnomad4 OTH exome

AF:

0.0515

GnomAD4 genome

AF:

0.0465

AC:

7081

AN:

152290

Hom.:

220

Cov.:

AF XY:

0.0464

AC XY:

3458

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.0328

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00932

Gnomad4 FIN

AF:

0.0937

Gnomad4 NFE

AF:

0.0710

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0602

Hom.:

Bravo

AF:

0.0417

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.3

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000085

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.010

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