Variant rs6435580 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.3756+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,378,736 control chromosomes in the GnomAD database, including 69,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5678 hom., cov: 32)

Exomes 𝑓: 0.31 ( 63789 hom. )

Consequence

CPS1
NM_001875.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.0550

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:

CPS1 (HGNC:):

CPS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 2-210658733-C-T is Benign according to our data. Variant chr2-210658733-C-T is described in ClinVar as [Benign]. Clinvar id is 258482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPS1	NM_001875.5 linkuse as main transcript	c.3756+45C>T		intron_variant		ENST00000233072.10	NP_001866.2	P31327-1A0A024R454Q6PEK7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPS1	ENST00000233072.10 linkuse as main transcript	c.3756+45C>T		intron_variant		1	NM_001875.5	ENSP00000233072.5		P31327-1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37933

AN:

151986

Hom.:

5683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0898

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.265

GnomAD3 exomes

AF:

0.282

AC:

69653

AN:

247160

Hom.:

10943

AF XY:

0.294

AC XY:

39345

AN XY:

133662

show subpopulations

Gnomad AFR exome

AF:

0.0819

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.353

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.297

GnomAD4 exome

AF:

0.312

AC:

383221

AN:

1226632

Hom.:

63789

Cov.:

AF XY:

0.316

AC XY:

196578

AN XY:

622484

show subpopulations

Gnomad4 AFR exome

AF:

0.0815

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.0694

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.349

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.249

AC:

37931

AN:

152104

Hom.:

5678

Cov.:

AF XY:

0.252

AC XY:

18752

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0897

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.307

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.324

Gnomad4 FIN

AF:

0.360

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.318

Hom.:

11190

Bravo

AF:

0.231

Asia WGS

AF:

0.195

AC:

681

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.72

CADD

Benign

8.8

DANN

Benign

0.47

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