Variant rs12718433 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001905.4(CTPS1):c.1094+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,584,336 control chromosomes in the GnomAD database, including 136,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10655 hom., cov: 32)

Exomes 𝑓: 0.41 ( 125572 hom. )

Consequence

CTPS1
NM_001905.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.50

Variant links:

Genes affected

CTPS1 (HGNC:2519): (CTP synthase 1) This gene encodes an enzyme responsible for the catalytic conversion of UTP (uridine triphosphate) to CTP (cytidine triphospate). This reaction is an important step in the biosynthesis of phospholipids and nucleic acids. Activity of this proten is important in the immune system, and loss of function of this gene has been associated with immunodeficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CTPS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-41001131-G-A is Benign according to our data. Variant chr1-41001131-G-A is described in ClinVar as [Benign]. Clinvar id is 402571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTPS1	NM_001905.4 link	c.1094+14G>A		intron_variant	Intron 10 of 18	ENST00000650070.2	NP_001896.2	P17812-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTPS1	ENST00000650070.2 link	c.1094+14G>A		intron_variant	Intron 10 of 18		NM_001905.4	ENSP00000497602.1		P17812-1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53344

AN:

151874

Hom.:

10653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.376

GnomAD3 exomes

AF:

0.406

AC:

93307

AN:

229616

Hom.:

19733

AF XY:

0.405

AC XY:

50628

AN XY:

124906

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.556

Gnomad ASJ exome

AF:

0.407

Gnomad EAS exome

AF:

0.406

Gnomad SAS exome

AF:

0.332

Gnomad FIN exome

AF:

0.413

Gnomad NFE exome

AF:

0.420

Gnomad OTH exome

AF:

0.426

GnomAD4 exome

AF:

0.414

AC:

593595

AN:

1432344

Hom.:

125572

Cov.:

AF XY:

0.412

AC XY:

293394

AN XY:

712958

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.547

Gnomad4 ASJ exome

AF:

0.401

Gnomad4 EAS exome

AF:

0.423

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.418

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.404

GnomAD4 genome

AF:

0.351

AC:

53353

AN:

151992

Hom.:

10655

Cov.:

AF XY:

0.356

AC XY:

26466

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.333

Gnomad4 FIN

AF:

0.425

Gnomad4 NFE

AF:

0.415

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.302

Hom.:

1516

Bravo

AF:

0.353

Asia WGS

AF:

0.335

AC:

1163

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 70. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Severe combined immunodeficiency due to CTPS1 deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.026

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over