Variant 2-210650334-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001875.5(CPS1):c.3405-29A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,580,844 control chromosomes in the GnomAD database, including 133,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.38 ( 11787 hom., cov: 32)

Exomes 𝑓: 0.41 ( 121790 hom. )

Consequence

CPS1
NM_001875.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 2.81

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but rather VUS (scored 5 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-210650334-A-T is Benign according to our data. Variant chr2-210650334-A-T is described in ClinVar as [Benign]. Clinvar id is 258479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-210650334-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 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.3405-29A>T		intron_variant		ENST00000233072.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPS1	ENST00000233072.10 linkuse as main transcript	c.3405-29A>T		intron_variant		1	NM_001875.5	P1	P31327-1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58362

AN:

151796

Hom.:

11785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.467

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.397

GnomAD3 exomes

AF:

0.425

AC:

106621

AN:

250998

Hom.:

23377

AF XY:

0.423

AC XY:

57456

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.503

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.520

Gnomad SAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.407

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.410

AC:

585457

AN:

1428928

Hom.:

121790

Cov.:

AF XY:

0.408

AC XY:

291302

AN XY:

713138

show subpopulations

Gnomad4 AFR exome

AF:

0.263

Gnomad4 AMR exome

AF:

0.502

Gnomad4 ASJ exome

AF:

0.340

Gnomad4 EAS exome

AF:

0.499

Gnomad4 SAS exome

AF:

0.414

Gnomad4 FIN exome

AF:

0.479

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.401

GnomAD4 genome

AF:

0.384

AC:

58395

AN:

151916

Hom.:

11787

Cov.:

AF XY:

0.389

AC XY:

28906

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.270

Gnomad4 AMR

AF:

0.467

Gnomad4 ASJ

AF:

0.333

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.421

Gnomad4 FIN

AF:

0.481

Gnomad4 NFE

AF:

0.411

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.387

Hom.:

2126

Bravo

AF:

0.378

Asia WGS

AF:

0.456

AC:

1584

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital hyperammonemia, type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.60

La Branchor

0.84

BranchPoint Hunter

5.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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