rs3027247

Variant names:

• chr17-8227549-A-C
• rs3027247
• NM_025099.6:c.*631T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-8227549-A-C
• chr17-8227549-A-G
• chr17-8227549-A-T

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.*631T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,166 control chromosomes in the GnomAD database, including 5,942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5921 hom., cov: 31)
  • Exomes 𝑓: 0.24 (21 hom.)
• Consequence: CTC1 NM_025099.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.271
• Publications: 33 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-8227549-A-C is Benign according to our data. Variant chr17-8227549-A-C is described in ClinVar as Benign. ClinVar VariationId is 326051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTC1	NM_025099.6	c.*631T>G		3_prime_UTR_variant	Exon 23 of 23	ENST00000651323.1	NP_079375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTC1	ENST00000651323.1	c.*631T>G		3_prime_UTR_variant	Exon 23 of 23		NM_025099.6	ENSP00000498499.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40876 AN: 151570 Hom.: 5913 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.241 AC: 115 AN: 478 Hom.: 21 Cov.: 0 AF XY: 0.254 AC XY: 70 AN XY: 276

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.269 AC: 7 AN: 26

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 4 AN: 8

South Asian (SAS) AF: 0.0556 AC: 1 AN: 18

European-Finnish (FIN) AF: 0.143 AC: 2 AN: 14

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.242 AC: 95 AN: 392

Other (OTH) AF: 0.313 AC: 5 AN: 16

GnomAD4 genome AF: 0.270 AC: 40921 AN: 151688 Hom.: 5921 Cov.: 31 AF XY: 0.269 AC XY: 19941 AN XY: 74138

African (AFR) AF: 0.200 AC: 8275 AN: 41308

American (AMR) AF: 0.415 AC: 6323 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1173 AN: 3466

East Asian (EAS) AF: 0.344 AC: 1765 AN: 5136

South Asian (SAS) AF: 0.196 AC: 945 AN: 4812

European-Finnish (FIN) AF: 0.223 AC: 2344 AN: 10510

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.283 AC: 19218 AN: 67904

Other (OTH) AF: 0.269 AC: 566 AN: 2108

Alfa AF: 0.285 Hom.: 28658

Bravo AF: 0.284

Asia WGS AF: 0.279 AC: 969 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dyskeratosis congenita Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.67
DANN	Benign	0.42
PhyloP100		-0.27

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: rs3027247; hg19: chr17-8130867; COSMIC: COSV59855113; COSMIC: COSV59855113;