rs12144160

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

severe combined immunodeficiency due to CTPS1 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

CTPS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001905.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CTPS1	NM_001905.4	MANE Select	c.1547-32A>G	intron	N/A	NP_001896.2
CTPS1	NM_001301237.2		c.1079-32A>G	intron	N/A	NP_001288166.1
CTPS1	NR_125440.2		n.1773-32A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CTPS1	ENST00000650070.2	MANE Select	c.1547-32A>G	intron	N/A	ENSP00000497602.1
CTPS1	ENST00000372616.1	TSL:2	c.1547-32A>G	intron	N/A	ENSP00000361699.1
CTPS1	ENST00000470271.6	TSL:3	c.1547-32A>G	intron	N/A	ENSP00000497901.2

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

GnomAD2 exomes

AF:

0.537

AC:

101740

AN:

189426

AF XY:

0.542

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 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

African (AFR)

AF:

0.237

AC:

7093

AN:

29920

American (AMR)

AF:

0.645

AC:

19227

AN:

29828

Ashkenazi Jewish (ASJ)

AF:

0.539

AC:

11504

AN:

21330

East Asian (EAS)

AF:

0.548

AC:

20797

AN:

37918

South Asian (SAS)

AF:

0.518

AC:

37899

AN:

73112

European-Finnish (FIN)

AF:

0.533

AC:

27139

AN:

50932

Middle Eastern (MID)

AF:

0.498

AC:

2684

AN:

5392

European-Non Finnish (NFE)

AF:

0.565

AC:

605196

AN:

1070838

Other (OTH)

AF:

0.547

AC:

30931

AN:

56530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

14502

29003

43505

58006

72508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17246

34492

51738

68984

86230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.475

AC:

72255

AN:

152140

Hom.:

18617

Cov.:

AF XY:

0.478

AC XY:

35575

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.260

AC:

10787

AN:

41524

American (AMR)

AF:

0.603

AC:

9214

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

1894

AN:

3472

East Asian (EAS)

AF:

0.546

AC:

2830

AN:

5182

South Asian (SAS)

AF:

0.525

AC:

2525

AN:

4806

European-Finnish (FIN)

AF:

0.533

AC:

5643

AN:

10578

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.554

AC:

37694

AN:

67980

Other (OTH)

AF:

0.511

AC:

1079

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1821

3643

5464

7286

9107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.481

Hom.:

4424

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

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.2

(source)

DANN

Benign

0.57

PhyloP100

-0.82

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over