chr2-210477778-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001122633.3(CPS1):c.-16+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,610,330 control chromosomes in the GnomAD database, including 209,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15891 hom., cov: 32)

Exomes 𝑓: 0.51 ( 194061 hom. )

Consequence

CPS1
NM_001122633.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.39

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:

LANCL1 (HGNC:6508): (LanC like glutathione S-transferase 1) This gene encodes a loosely associated peripheral membrane protein related to the LanC family of bacterial membrane-associated proteins involved in the biosynthesis of antimicrobial peptides. This protein may play a role as a peptide-modifying enzyme component in eukaryotic cells. Previously considered a member of the G-protein-coupled receptor superfamily, this protein is now in the LanC family. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2008]

LANCL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-210477778-G-A is Benign according to our data. Variant chr2-210477778-G-A is described in ClinVar as [Benign]. Clinvar id is 137026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-210477778-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
CPS1	NM_001122633.3 link	c.-16+12G>A	intron_variant	Intron 1 of 38	NP_001116105.2	P31327-1Q6PEK7
CPS1	NM_001369257.1 link	c.-136+12G>A	intron_variant	Intron 1 of 39	NP_001356186.1
LANCL1	XM_005246243.3 link	c.-309C>T	upstream_gene_variant		XP_005246300.1	A0A024R3Z5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CPS1	ENST00000430249.7 link	c.3+12G>A	intron_variant	Intron 1 of 38	1	ENSP00000402608.2	P31327-3
CPS1	ENST00000673510.1 link	c.-136+12G>A	intron_variant	Intron 1 of 39		ENSP00000500537.1	P31327-1
CPS1	ENST00000673630.1 link	c.-250+12G>A	intron_variant	Intron 1 of 39		ENSP00000501073.1	P31327-1

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66809

AN:

151888

Hom.:

15891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.593

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.590

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.391

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.443

GnomAD3 exomes

AF:

0.512

AC:

126630

AN:

247172

Hom.:

33705

AF XY:

0.514

AC XY:

68998

AN XY:

134292

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.609

Gnomad ASJ exome

AF:

0.427

Gnomad EAS exome

AF:

0.628

Gnomad SAS exome

AF:

0.591

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.493

Gnomad OTH exome

AF:

0.487

GnomAD4 exome

AF:

0.512

AC:

746332

AN:

1458324

Hom.:

194061

Cov.:

AF XY:

0.513

AC XY:

372321

AN XY:

725490

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.597

Gnomad4 ASJ exome

AF:

0.433

Gnomad4 EAS exome

AF:

0.603

Gnomad4 SAS exome

AF:

0.586

Gnomad4 FIN exome

AF:

0.485

Gnomad4 NFE exome

AF:

0.512

Gnomad4 OTH exome

AF:

0.488

GnomAD4 genome

AF:

0.440

AC:

66819

AN:

152006

Hom.:

15891

Cov.:

AF XY:

0.443

AC XY:

32933

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.512

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.610

Gnomad4 SAS

AF:

0.589

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.503

Gnomad4 OTH

AF:

0.446

Alfa

AF:

0.465

Hom.:

4848

Bravo

AF:

0.439

Asia WGS

AF:

0.550

AC:

1910

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 25, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Congenital hyperammonemia, type I

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.24

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

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