rs3027234

Variant names:

• chr17-8232774-C-T
• rs3027234
• NM_025099.6:c.1945+132G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-8232774-C-T
• chr17-8232774-C-A
• chr17-8232774-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025099.6(CTC1):​c.1945+132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,220,852 control chromosomes in the GnomAD database, including 25,361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2220 hom., cov: 32)
  • Exomes 𝑓: 0.20 (23141 hom.)
• Consequence: CTC1 NM_025099.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.282
• Publications: 71 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):

• 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Coats plus syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-8232774-C-T is Benign according to our data. Variant chr17-8232774-C-T is described in ClinVar as Benign. ClinVar VariationId is 1233975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTC1	NM_025099.6	MANE Select	c.1945+132G>A		intron	N/A	NP_079375.3
	CTC1	NM_001411067.1		c.1945+132G>A		intron	N/A	NP_001397996.1	J3KSZ1
	CTC1	NR_046431.2		n.1860+132G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTC1	ENST00000651323.1	MANE Select	c.1945+132G>A		intron	N/A	ENSP00000498499.1	Q2NKJ3-1
	CTC1	ENST00000932859.1		c.1945+132G>A		intron	N/A	ENSP00000602918.1
	CTC1	ENST00000968384.1		c.1945+132G>A		intron	N/A	ENSP00000638443.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23739 AN: 152082 Hom.: 2219 Cov.: 32

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.201 AC: 214365 AN: 1068650 Hom.: 23141 Cov.: 14 AF XY: 0.199 AC XY: 107083 AN XY: 537036

African (AFR) AF: 0.0606 AC: 1500 AN: 24760

American (AMR) AF: 0.105 AC: 3324 AN: 31606

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 4118 AN: 18774

East Asian (EAS) AF: 0.0333 AC: 1247 AN: 37492

South Asian (SAS) AF: 0.122 AC: 7958 AN: 65344

European-Finnish (FIN) AF: 0.158 AC: 7863 AN: 49830

Middle Eastern (MID) AF: 0.185 AC: 751 AN: 4050

European-Non Finnish (NFE) AF: 0.226 AC: 178934 AN: 790352

Other (OTH) AF: 0.187 AC: 8670 AN: 46442

GnomAD4 genome AF: 0.156 AC: 23745 AN: 152202 Hom.: 2220 Cov.: 32 AF XY: 0.151 AC XY: 11230 AN XY: 74408

African (AFR) AF: 0.0664 AC: 2759 AN: 41546

American (AMR) AF: 0.138 AC: 2117 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3470

East Asian (EAS) AF: 0.0433 AC: 224 AN: 5178

South Asian (SAS) AF: 0.110 AC: 532 AN: 4826

European-Finnish (FIN) AF: 0.152 AC: 1605 AN: 10586

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15185 AN: 67998

Other (OTH) AF: 0.148 AC: 311 AN: 2108

Alfa AF: 0.189 Hom.: 5558

Bravo AF: 0.152

Asia WGS AF: 0.0710 AC: 245 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3027234;

hg19: chr17-8136092;