rs9900520

Variant names:

• chr17-8247845-A-C
• rs9900520
• NM_025099.6:c.33+159T>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.33+159T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 679,714 control chromosomes in the GnomAD database, including 290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (205 hom., cov: 31)
  • Exomes 𝑓: 0.0056 (85 hom.)
• Consequence: CTC1 NM_025099.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.335
• Publications: 0 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]

PFAS (HGNC:8863): (phosphoribosylformylglycinamidine synthase) Purines are necessary for many cellular processes, including DNA replication, transcription, and energy metabolism. Ten enzymatic steps are required to synthesize inosine monophosphate (IMP) in the de novo pathway of purine biosynthesis. The enzyme encoded by this gene catalyzes the fourth step of IMP biosynthesis. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 17-8247845-A-C is Benign according to our data. Variant chr17-8247845-A-C is described in ClinVar as [Benign]. Clinvar id is 1271918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTC1	NM_025099.6	c.33+159T>G		intron_variant	Intron 1 of 22	ENST00000651323.1	NP_079375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTC1	ENST00000651323.1	c.33+159T>G		intron_variant	Intron 1 of 22		NM_025099.6	ENSP00000498499.1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4609 AN: 152182 Hom.: 205 Cov.: 31

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00213

Gnomad OTH AF: 0.0301

GnomAD4 exome AF: 0.00563 AC: 2970 AN: 527414 Hom.: 85 Cov.: 6 AF XY: 0.00478 AC XY: 1333 AN XY: 278618

African (AFR) AF: 0.103 AC: 1402 AN: 13596

American (AMR) AF: 0.0143 AC: 328 AN: 22930

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 166 AN: 15642

East Asian (EAS) AF: 0.00 AC: 0 AN: 31102

South Asian (SAS) AF: 0.000500 AC: 26 AN: 52002

European-Finnish (FIN) AF: 0.0000657 AC: 3 AN: 45648

Middle Eastern (MID) AF: 0.0270 AC: 94 AN: 3484

European-Non Finnish (NFE) AF: 0.00189 AC: 595 AN: 314718

Other (OTH) AF: 0.0126 AC: 356 AN: 28292

GnomAD4 genome AF: 0.0303 AC: 4617 AN: 152300 Hom.: 205 Cov.: 31 AF XY: 0.0289 AC XY: 2153 AN XY: 74486

African (AFR) AF: 0.0981 AC: 4077 AN: 41564

American (AMR) AF: 0.0179 AC: 274 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00213 AC: 145 AN: 68026

Other (OTH) AF: 0.0298 AC: 63 AN: 2116

Alfa AF: 0.0231 Hom.: 27

Bravo AF: 0.0351

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		0.34
PromoterAI		-0.043	Neutral
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: rs9900520; hg19: chr17-8151163;