rs4233981

Positions:

• chr2-210664654-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001875.5(CPS1):​c.4002+1457G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,042 control chromosomes in the GnomAD database, including 43,501 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (43501 hom., cov: 31)
• Consequence: CPS1 NM_001875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPS1	NM_001875.5	c.4002+1457G>C		intron_variant		ENST00000233072.10	NP_001866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPS1	ENST00000233072.10	c.4002+1457G>C		intron_variant		1	NM_001875.5	ENSP00000233072.5

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113813 AN: 151924 Hom.: 43473 Cov.: 31

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.735

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.749 AC: 113894 AN: 152042 Hom.: 43501 Cov.: 31 AF XY: 0.751 AC XY: 55800 AN XY: 74342

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.732

Alfa AF: 0.782 Hom.: 5848

Bravo AF: 0.735

Asia WGS AF: 0.685 AC: 2383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs4233981; hg19: chr2-211529378;