rs12144160

Variant names:

• chr1-41009413-A-G
• rs12144160
• NM_001905.4:c.1547-32A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-41009413-A-G
• chr1-41009413-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.823
• Publications: 11 publications found

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)

ACMG classification

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 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	c.1547-32A>G		intron_variant	Intron 16 of 18	ENST00000650070.2	NP_001896.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTPS1	ENST00000650070.2	c.1547-32A>G		intron_variant	Intron 16 of 18		NM_001905.4	ENSP00000497602.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72202 AN: 152020 Hom.: 18608 Cov.: 32

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

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.: 31 AF XY: 0.553 AC XY: 374383 AN XY: 676886

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

GnomAD4 genome AF: 0.475 AC: 72255 AN: 152140 Hom.: 18617 Cov.: 32 AF XY: 0.478 AC XY: 35575 AN XY: 74368

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

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		-0.82
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: rs12144160; hg19: chr1-41475085; COSMIC: COSV65452641;