rs7523029

Variant names:

• chr1-40984187-T-C
• rs7523029
• NM_001905.4:c.167-634T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001905.4(CTPS1):​c.167-634T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,058 control chromosomes in the GnomAD database, including 6,305 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6305 hom., cov: 33)
• Consequence: CTPS1 NM_001905.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTPS1	NM_001905.4	c.167-634T>C		intron_variant	Intron 2 of 18	ENST00000650070.2	NP_001896.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTPS1	ENST00000650070.2	c.167-634T>C		intron_variant	Intron 2 of 18		NM_001905.4	ENSP00000497602.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42602 AN: 151940 Hom.: 6290 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.257

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.281 AC: 42655 AN: 152058 Hom.: 6305 Cov.: 33 AF XY: 0.277 AC XY: 20571 AN XY: 74292

African (AFR) AF: 0.315 AC: 13054 AN: 41496

American (AMR) AF: 0.216 AC: 3299 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 841 AN: 3468

East Asian (EAS) AF: 0.110 AC: 561 AN: 5102

South Asian (SAS) AF: 0.155 AC: 749 AN: 4822

European-Finnish (FIN) AF: 0.293 AC: 3090 AN: 10560

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20228 AN: 68008

Other (OTH) AF: 0.255 AC: 539 AN: 2112

Alfa AF: 0.290 Hom.: 17842

Bravo AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.85
PhyloP100		0.17
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: rs7523029; hg19: chr1-41449859;