Variant rs12144160 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.1547-32A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,527,940 control chromosomes in the GnomAD database, including 232,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18617 hom., cov: 32)

Exomes 𝑓: 0.55 ( 213902 hom. )

Consequence

CTPS1
NM_001905.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.823

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-41009413-A-G is Benign according to our data. Variant chr1-41009413-A-G is described in ClinVar as [Benign]. Clinvar id is 1255416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTPS1	NM_001905.4 link	c.1547-32A>G		intron_variant	Intron 16 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.1547-32A>G		intron_variant	Intron 16 of 18		NM_001905.4	ENSP00000497602.1		P17812-1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72202

AN:

152020

Hom.:

18608

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.603

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.513

GnomAD3 exomes

AF:

0.537

AC:

101740

AN:

189426

Hom.:

28180

AF XY:

0.542

AC XY:

55063

AN XY:

101548

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.651

Gnomad ASJ exome

AF:

0.541

Gnomad EAS exome

AF:

0.541

Gnomad SAS exome

AF:

0.518

Gnomad FIN exome

AF:

0.524

Gnomad NFE exome

AF:

0.560

Gnomad OTH exome

AF:

0.560

GnomAD4 exome

AF:

0.554

AC:

762470

AN:

1375800

Hom.:

213902

Cov.:

AF XY:

0.553

AC XY:

374383

AN XY:

676886

show subpopulations

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.645

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.548

Gnomad4 SAS exome

AF:

0.518

Gnomad4 FIN exome

AF:

0.533

Gnomad4 NFE exome

AF:

0.565

Gnomad4 OTH exome

AF:

0.547

GnomAD4 genome

AF:

0.475

AC:

72255

AN:

152140

Hom.:

18617

Cov.:

AF XY:

0.478

AC XY:

35575

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.603

Gnomad4 ASJ

AF:

0.546

Gnomad4 EAS

AF:

0.546

Gnomad4 SAS

AF:

0.525

Gnomad4 FIN

AF:

0.533

Gnomad4 NFE

AF:

0.554

Gnomad4 OTH

AF:

0.511

Alfa

AF:

0.486

Hom.:

4391

Bravo

AF:

0.472

Asia WGS

AF:

0.501

AC:

1744

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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 78% of patients studied by a panel of primary immunodeficiencies. Number of patients: 75. Only high quality variants are reported. -

Severe combined immunodeficiency due to CTPS1 deficiency

Benign:1

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

-0.89

CADD

Benign

2.2

DANN

Benign

0.57

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