rs11651199

Positions:

• chr17-8239326-G-A
• chr17-8239326-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTC1	NM_025099.6	c.198-697C>T		intron_variant		ENST00000651323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTC1	ENST00000651323.1	c.198-697C>T		intron_variant			NM_025099.6	P1

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

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.143

Alfa AF: 0.186 Hom.: 1434

Bravo AF: 0.147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs11651199; hg19: chr17-8142644; COSMIC: COSV59855192; COSMIC: COSV59855192;