Variant chr2-210477748-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000430249.7(CPS1):c.-16G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,613,276 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 31 hom., cov: 32)

Exomes 𝑓: 0.014 ( 241 hom. )

Consequence

CPS1
ENST00000430249.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.601

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-210477748-G-A is Benign according to our data. Variant chr2-210477748-G-A is described in ClinVar as [Benign]. Clinvar id is 380167.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-210477748-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0133 (2023/152270) while in subpopulation NFE AF= 0.0153 (1038/68032). AF 95% confidence interval is 0.0145. There are 31 homozygotes in gnomad4. There are 1119 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPS1	NM_001122633.3 linkuse as main transcript	c.-34G>A		5_prime_UTR_variant	1/39
CPS1	NM_001369257.1 linkuse as main transcript	c.-154G>A		5_prime_UTR_variant	1/40

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Appris	UniProt
CPS1	ENST00000430249.7 linkuse as main transcript	c.-16G>A	5_prime_UTR_variant	1/39	1		P31327-3
CPS1	ENST00000673510.1 linkuse as main transcript	c.-154G>A	5_prime_UTR_variant	1/40		P1	P31327-1
CPS1	ENST00000673630.1 linkuse as main transcript	c.-268G>A	5_prime_UTR_variant	1/40		P1	P31327-1
CPS1	ENST00000673711.1 linkuse as main transcript	c.-34G>A	5_prime_UTR_variant	1/39		P1	P31327-1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2023

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00897

Gnomad ASJ

AF:

0.0600

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0466

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.0152

AC:

3784

AN:

248272

Hom.:

AF XY:

0.0150

AC XY:

2025

AN XY:

134912

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.00657

Gnomad ASJ exome

AF:

0.0598

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.00164

Gnomad FIN exome

AF:

0.0424

Gnomad NFE exome

AF:

0.0165

Gnomad OTH exome

AF:

0.0186

GnomAD4 exome

AF:

0.0138

AC:

20148

AN:

1461006

Hom.:

241

Cov.:

AF XY:

0.0136

AC XY:

9920

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00674

Gnomad4 ASJ exome

AF:

0.0604

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00177

Gnomad4 FIN exome

AF:

0.0383

Gnomad4 NFE exome

AF:

0.0134

Gnomad4 OTH exome

AF:

0.0161

GnomAD4 genome

AF:

0.0133

AC:

2023

AN:

152270

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1119

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.00896

Gnomad4 ASJ

AF:

0.0600

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0466

Gnomad4 NFE

AF:

0.0153

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0100

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 14, 2016

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.1

DANN

Benign

0.68

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