17-8239326-G-A

Variant names:

• chr17-8239326-G-A
• rs11651199
• NM_025099.6:c.198-697C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025099.6(CTC1):​c.198-697C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,000 control chromosomes in the GnomAD database, including 2,201 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2201 hom., cov: 31)
• Consequence: CTC1 NM_025099.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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.198-697C>T		intron	N/A	NP_079375.3
	CTC1	NM_001411067.1		c.198-697C>T		intron	N/A	NP_001397996.1	J3KSZ1
	CTC1	NR_046431.2		n.218-697C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTC1	ENST00000651323.1	MANE Select	c.198-697C>T		intron	N/A	ENSP00000498499.1	Q2NKJ3-1
	CTC1	ENST00000932859.1		c.198-697C>T		intron	N/A	ENSP00000602918.1
	CTC1	ENST00000968384.1		c.198-697C>T		intron	N/A	ENSP00000638443.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22915 AN: 151882 Hom.: 2201 Cov.: 31

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.151 AC: 22914 AN: 152000 Hom.: 2201 Cov.: 31 AF XY: 0.146 AC XY: 10838 AN XY: 74298

African (AFR) AF: 0.0476 AC: 1973 AN: 41466

American (AMR) AF: 0.136 AC: 2073 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3468

East Asian (EAS) AF: 0.0396 AC: 205 AN: 5180

South Asian (SAS) AF: 0.110 AC: 532 AN: 4822

European-Finnish (FIN) AF: 0.150 AC: 1580 AN: 10554

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

European-Non Finnish (NFE) AF: 0.224 AC: 15239 AN: 67964

Other (OTH) AF: 0.143 AC: 301 AN: 2108

Alfa AF: 0.187 Hom.: 2076

Bravo AF: 0.147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.88
PhyloP100		-0.065
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: rs11651199; hg19: chr17-8142644; COSMIC: COSV59855192; COSMIC: COSV59855192;