17-8227905-C-T

Variant names:

• chr17-8227905-C-T
• rs3027246
• NM_025099.6:c.*275G>A

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.*275G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 347,944 control chromosomes in the GnomAD database, including 5,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2183 hom., cov: 31)
  • Exomes 𝑓: 0.18 (3706 hom.)
• Consequence: CTC1 NM_025099.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.246
• Publications: 14 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.81).
• BP6: Variant 17-8227905-C-T is Benign according to our data. Variant chr17-8227905-C-T is described in ClinVar as Benign. ClinVar VariationId is 326056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 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.*275G>A		3_prime_UTR	Exon 23 of 23	NP_079375.3
	CTC1	NM_001411067.1		c.*275G>A		3_prime_UTR	Exon 21 of 21	NP_001397996.1	J3KSZ1
	CTC1	NR_046431.2		n.3779G>A		non_coding_transcript_exon	Exon 22 of 22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTC1	ENST00000651323.1	MANE Select	c.*275G>A		3_prime_UTR	Exon 23 of 23	ENSP00000498499.1	Q2NKJ3-1
	CTC1	ENST00000932859.1		c.*275G>A		3_prime_UTR	Exon 23 of 23	ENSP00000602918.1
	CTC1	ENST00000968384.1		c.*275G>A		3_prime_UTR	Exon 23 of 23	ENSP00000638443.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22879 AN: 151986 Hom.: 2183 Cov.: 31

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.176 AC: 34378 AN: 195840 Hom.: 3706 Cov.: 0 AF XY: 0.174 AC XY: 17820 AN XY: 102190

African (AFR) AF: 0.0429 AC: 308 AN: 7172

American (AMR) AF: 0.116 AC: 1166 AN: 10012

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 1322 AN: 6276

East Asian (EAS) AF: 0.0266 AC: 376 AN: 14120

South Asian (SAS) AF: 0.110 AC: 2086 AN: 19004

European-Finnish (FIN) AF: 0.148 AC: 1336 AN: 9038

Middle Eastern (MID) AF: 0.187 AC: 163 AN: 870

European-Non Finnish (NFE) AF: 0.217 AC: 25607 AN: 117890

Other (OTH) AF: 0.176 AC: 2014 AN: 11458

GnomAD4 genome AF: 0.150 AC: 22878 AN: 152104 Hom.: 2183 Cov.: 31 AF XY: 0.145 AC XY: 10812 AN XY: 74362

African (AFR) AF: 0.0475 AC: 1972 AN: 41520

American (AMR) AF: 0.135 AC: 2063 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3468

East Asian (EAS) AF: 0.0384 AC: 198 AN: 5160

South Asian (SAS) AF: 0.110 AC: 528 AN: 4816

European-Finnish (FIN) AF: 0.151 AC: 1603 AN: 10590

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15205 AN: 67962

Other (OTH) AF: 0.144 AC: 304 AN: 2106

Alfa AF: 0.196 Hom.: 4169

Bravo AF: 0.146

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Dyskeratosis congenita (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.6
DANN	Benign	0.61
PhyloP100		-0.25
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

Other links and lift over

dbSNP: rs3027246; hg19: chr17-8131223; COSMIC: COSV59855122; COSMIC: COSV59855122;