chr2-210591915-C-T

Position:

chr2-210591915-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001875.5(CPS1):c.1032C>T(p.Thr344=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,610,134 control chromosomes in the GnomAD database, including 262,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26997 hom., cov: 32)

Exomes 𝑓: 0.57 ( 235876 hom. )

Consequence

CPS1
NM_001875.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.678

Variant links:

Genes affected

CPS1 (HGNC:2323): (carbamoyl-phosphate synthase 1) The mitochondrial enzyme encoded by this gene catalyzes synthesis of carbamoyl phosphate from ammonia and bicarbonate. This reaction is the first committed step of the urea cycle, which is important in the removal of excess urea from cells. The encoded protein may also represent a core mitochondrial nucleoid protein. Three transcript variants encoding different isoforms have been found for this gene. The shortest isoform may not be localized to the mitochondrion. Mutations in this gene have been associated with carbamoyl phosphate synthetase deficiency, susceptibility to persistent pulmonary hypertension, and susceptibility to venoocclusive disease after bone marrow transplantation.[provided by RefSeq, May 2010]

CPS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 2-210591915-C-T is Benign according to our data. Variant chr2-210591915-C-T is described in ClinVar as [Benign]. Clinvar id is 128850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-210591915-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.678 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPS1	NM_001875.5 linkuse as main transcript	c.1032C>T	p.Thr344=	synonymous_variant	10/38	ENST00000233072.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPS1	ENST00000233072.10 linkuse as main transcript	c.1032C>T	p.Thr344=	synonymous_variant	10/38	1	NM_001875.5	P1	P31327-1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

89923

AN:

151206

Hom.:

26962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.532

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.636

Gnomad MID

AF:

0.643

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.589

GnomAD3 exomes

AF:

0.571

AC:

142506

AN:

249724

Hom.:

41137

AF XY:

0.576

AC XY:

77695

AN XY:

134988

show subpopulations

Gnomad AFR exome

AF:

0.664

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.618

Gnomad EAS exome

AF:

0.547

Gnomad SAS exome

AF:

0.601

Gnomad FIN exome

AF:

0.633

Gnomad NFE exome

AF:

0.566

Gnomad OTH exome

AF:

0.580

GnomAD4 exome

AF:

0.567

AC:

827090

AN:

1458812

Hom.:

235876

Cov.:

AF XY:

0.570

AC XY:

413364

AN XY:

725806

show subpopulations

Gnomad4 AFR exome

AF:

0.676

Gnomad4 AMR exome

AF:

0.483

Gnomad4 ASJ exome

AF:

0.608

Gnomad4 EAS exome

AF:

0.551

Gnomad4 SAS exome

AF:

0.605

Gnomad4 FIN exome

AF:

0.627

Gnomad4 NFE exome

AF:

0.559

Gnomad4 OTH exome

AF:

0.585

GnomAD4 genome

AF:

0.595

AC:

90009

AN:

151322

Hom.:

26997

Cov.:

AF XY:

0.597

AC XY:

44121

AN XY:

73902

show subpopulations

Gnomad4 AFR

AF:

0.661

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.614

Gnomad4 EAS

AF:

0.567

Gnomad4 SAS

AF:

0.616

Gnomad4 FIN

AF:

0.636

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.591

Alfa

AF:

0.577

Hom.:

12968

Bravo

AF:

0.585

Asia WGS

AF:

0.629

AC:

2184

AN:

3476

EpiCase

AF:

0.574

EpiControl

AF:

0.579

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 10, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 25, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Congenital hyperammonemia, type I

Benign:6

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Jun 28, 2017	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

8.7

DANN

Benign

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over