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GeneBe

rs5030799

Positions:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001905.4(CTPS1):ā€‹c.501A>Gā€‹(p.Gln167=) 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 (ā˜…).

Frequency

Genomes: š‘“ 0.022 ( 62 hom., cov: 32)
Exomes š‘“: 0.017 ( 566 hom. )

Consequence

CTPS1
NM_001905.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.742
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-40988656-A-G is Benign according to our data. Variant chr1-40988656-A-G is described in ClinVar as [Benign]. Clinvar id is 475187.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.742 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CTPS1NM_001905.4 linkuse as main transcriptc.501A>G p.Gln167= synonymous_variant 5/19 ENST00000650070.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTPS1ENST00000650070.2 linkuse as main transcriptc.501A>G p.Gln167= synonymous_variant 5/19 NM_001905.4 P1P17812-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0220
AC:
3354
AN:
152166
Hom.:
64
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.0254
AC:
6387
AN:
251454
Hom.:
175
AF XY:
0.0269
AC XY:
3659
AN XY:
135900
show subpopulations
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 SAS exome
AF:
0.0662
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0399
Gnomad4 AMR exome
AF:
0.00845
Gnomad4 ASJ exome
AF:
0.0218
Gnomad4 EAS exome
AF:
0.0989
Gnomad4 SAS exome
AF:
0.0659
Gnomad4 FIN exome
AF:
0.00678
Gnomad4 NFE exome
AF:
0.00958
Gnomad4 OTH exome
AF:
0.0212
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0220
AC:
3356
AN:
152286
Hom.:
62
Cov.:
32
AF XY:
0.0232
AC XY:
1729
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0359
Gnomad4 AMR
AF:
0.0117
Gnomad4 ASJ
AF:
0.0202
Gnomad4 EAS
AF:
0.0920
Gnomad4 SAS
AF:
0.0672
Gnomad4 FIN
AF:
0.00725
Gnomad4 NFE
AF:
0.00983
Gnomad4 OTH
AF:
0.0265
Alfa
AF:
0.0147
Hom.:
14
Bravo
AF:
0.0228
Asia WGS
AF:
0.0790
AC:
272
AN:
3478
EpiCase
AF:
0.0116
EpiControl
AF:
0.0140

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Severe combined immunodeficiency due to CTPS1 deficiency Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
7.0
DANN
Benign
0.44
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5030799; hg19: chr1-41454328; COSMIC: COSV65451784; COSMIC: COSV65451784; API