rs3027235

Variant names:

• chr17-8232128-G-A
• rs3027235
• NM_025099.6:c.2160C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000651323.1(CTC1):​c.2160C>T​(p.Thr720Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,528,728 control chromosomes in the GnomAD database, including 665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (221 hom., cov: 32)
  • Exomes 𝑓: 0.018 (444 hom.)
• Consequence: CTC1 ENST00000651323.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.764
• Publications: 4 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-8232128-G-A is Benign according to our data. Variant chr17-8232128-G-A is described in ClinVar as Benign. ClinVar VariationId is 326074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.764 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651323.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTC1	NM_025099.6	MANE Select	c.2160C>T	p.Thr720Thr	synonymous	Exon 13 of 23	NP_079375.3
	CTC1	NM_001411067.1		c.2160C>T	p.Thr720Thr	synonymous	Exon 13 of 21	NP_001397996.1
	CTC1	NR_046431.2		n.2075C>T		non_coding_transcript_exon	Exon 13 of 22

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTC1	ENST00000651323.1	MANE Select	c.2160C>T	p.Thr720Thr	synonymous	Exon 13 of 23	ENSP00000498499.1
	CTC1	ENST00000581729.2	TSL:3	c.2160C>T	p.Thr720Thr	synonymous	Exon 13 of 21	ENSP00000462720.2
	CTC1	ENST00000580299.2	TSL:5	c.2160C>T	p.Thr720Thr	synonymous	Exon 13 of 21	ENSP00000462607.2

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5901 AN: 152152 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0306

GnomAD2 exomes AF: 0.0301 AC: 4983 AN: 165530 AF XY: 0.0266

Gnomad AFR exome AF: 0.0755

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.0393

Gnomad EAS exome AF: 0.00831

Gnomad FIN exome AF: 0.00563

Gnomad NFE exome AF: 0.0141

Gnomad OTH exome AF: 0.0253

GnomAD4 exome AF: 0.0177 AC: 24301 AN: 1376458 Hom.: 444 Cov.: 32 AF XY: 0.0171 AC XY: 11615 AN XY: 677292

African (AFR) AF: 0.0772 AC: 2346 AN: 30378

American (AMR) AF: 0.108 AC: 3151 AN: 29156

Ashkenazi Jewish (ASJ) AF: 0.0373 AC: 754 AN: 20206

East Asian (EAS) AF: 0.00979 AC: 381 AN: 38924

South Asian (SAS) AF: 0.0134 AC: 954 AN: 71172

European-Finnish (FIN) AF: 0.00635 AC: 317 AN: 49908

Middle Eastern (MID) AF: 0.0137 AC: 73 AN: 5342

European-Non Finnish (NFE) AF: 0.0140 AC: 15058 AN: 1074726

Other (OTH) AF: 0.0224 AC: 1267 AN: 56646

GnomAD4 genome AF: 0.0388 AC: 5914 AN: 152270 Hom.: 221 Cov.: 32 AF XY: 0.0397 AC XY: 2958 AN XY: 74456

African (AFR) AF: 0.0747 AC: 3103 AN: 41534

American (AMR) AF: 0.0932 AC: 1425 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3470

East Asian (EAS) AF: 0.0102 AC: 53 AN: 5186

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4822

European-Finnish (FIN) AF: 0.00480 AC: 51 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0152 AC: 1033 AN: 68024

Other (OTH) AF: 0.0346 AC: 73 AN: 2112

Alfa AF: 0.0255 Hom.: 179

Bravo AF: 0.0456

Asia WGS AF: 0.0410 AC: 142 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Cerebroretinal microangiopathy with calcifications and cysts 1 (2)
-	-	2	Dyskeratosis congenita (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.5
DANN	Benign	0.31
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3027235; hg19: chr17-8135446; COSMIC: COSV107326318; COSMIC: COSV107326318;