rs7523029

chr1-40984187-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CTPS1	NM_001905.4	c.167-634T>C		intron_variant		ENST00000650070.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTPS1	ENST00000650070.2	c.167-634T>C		intron_variant			NM_001905.4	P1

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

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.255

Alfa AF: 0.290 Hom.: 12919

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

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

Other links and lift over

dbSNP: rs7523029; hg19: chr1-41449859;