rs5030799

Variant names:

• chr1-40988656-A-G
• rs5030799
• NM_001905.4:c.501A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-40988656-A-G
• chr1-40988656-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001905.4(CTPS1):​c.501A>G​(p.Gln167Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,614,002 control chromosomes in the GnomAD database, including 628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (62 hom., cov: 32)
  • Exomes 𝑓: 0.017 (566 hom.)
• Consequence: CTPS1 NM_001905.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.742
• Publications: 10 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):

• combined immunodeficiency due to CTPS1 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-40988656-A-G is Benign according to our data. Variant chr1-40988656-A-G is described in ClinVar as Benign. ClinVar VariationId is 475187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.742 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0852 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTPS1	NM_001905.4	MANE Select	c.501A>G	p.Gln167Gln	synonymous	Exon 5 of 19	NP_001896.2	P17812-1
	CTPS1	NM_001301237.2		c.33A>G	p.Gln11Gln	synonymous	Exon 1 of 15	NP_001288166.1	B4E1E0
	CTPS1	NR_125440.2		n.648A>G		non_coding_transcript_exon	Exon 5 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTPS1	ENST00000650070.2	MANE Select	c.501A>G	p.Gln167Gln	synonymous	Exon 5 of 19	ENSP00000497602.1	P17812-1
	CTPS1	ENST00000372616.1	TSL:2	c.501A>G	p.Gln167Gln	synonymous	Exon 4 of 18	ENSP00000361699.1	P17812-1
	CTPS1	ENST00000470271.6	TSL:3	c.501A>G	p.Gln167Gln	synonymous	Exon 5 of 19	ENSP00000497901.2	P17812-1

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3354 AN: 152166 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.0659

Gnomad FIN AF: 0.00725

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00983

Gnomad OTH AF: 0.0263

GnomAD2 exomes AF: 0.0254 AC: 6387 AN: 251454 AF XY: 0.0269

Gnomad AFR exome AF: 0.0373

Gnomad AMR exome AF: 0.00763

Gnomad ASJ exome AF: 0.0200

Gnomad EAS exome AF: 0.0979

Gnomad FIN exome AF: 0.00688

Gnomad NFE exome AF: 0.0108

Gnomad OTH exome AF: 0.0176

GnomAD4 exome AF: 0.0167 AC: 24433 AN: 1461716 Hom.: 566 Cov.: 30 AF XY: 0.0183 AC XY: 13283 AN XY: 727162

African (AFR) AF: 0.0399 AC: 1334 AN: 33472

American (AMR) AF: 0.00845 AC: 378 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0218 AC: 570 AN: 26120

East Asian (EAS) AF: 0.0989 AC: 3926 AN: 39690

South Asian (SAS) AF: 0.0659 AC: 5684 AN: 86232

European-Finnish (FIN) AF: 0.00678 AC: 362 AN: 53418

Middle Eastern (MID) AF: 0.0425 AC: 245 AN: 5768

European-Non Finnish (NFE) AF: 0.00958 AC: 10654 AN: 1111902

Other (OTH) AF: 0.0212 AC: 1280 AN: 60390

GnomAD4 genome AF: 0.0220 AC: 3356 AN: 152286 Hom.: 62 Cov.: 32 AF XY: 0.0232 AC XY: 1729 AN XY: 74460

African (AFR) AF: 0.0359 AC: 1493 AN: 41554

American (AMR) AF: 0.0117 AC: 179 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.0920 AC: 476 AN: 5174

South Asian (SAS) AF: 0.0672 AC: 324 AN: 4822

European-Finnish (FIN) AF: 0.00725 AC: 77 AN: 10616

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00983 AC: 669 AN: 68024

Other (OTH) AF: 0.0265 AC: 56 AN: 2116

Alfa AF: 0.0162 Hom.: 69

Bravo AF: 0.0228

Asia WGS AF: 0.0790 AC: 272 AN: 3478

EpiCase AF: 0.0116

EpiControl AF: 0.0140

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Combined immunodeficiency due to CTPS1 deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.0
DANN	Benign	0.44
PhyloP100		0.74
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs5030799; hg19: chr1-41454328; COSMIC: COSV65451784; COSMIC: COSV65451784;