2-210556540-G-T

Variant names:

• chr2-210556540-G-T
• rs6732642
• ENST00000430249.7:c.4-179G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001369256.1(CPS1):​c.19-179G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000227 in 1,322,458 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CPS1 NM_001369256.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• carbamoyl phosphate synthetase I deficiency disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369256.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPS1	NM_001369256.1		c.19-179G>T		intron	N/A	NP_001356185.1
	CPS1	NM_001122633.3		c.-15-179G>T		intron	N/A	NP_001116105.2	P31327-1
	CPS1	NM_001369257.1		c.-15-179G>T		intron	N/A	NP_001356186.1	P31327-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPS1	ENST00000430249.7	TSL:1	c.4-179G>T		intron	N/A	ENSP00000402608.2	P31327-3
	CPS1	ENST00000673510.1		c.-15-179G>T		intron	N/A	ENSP00000500537.1	P31327-1
	CPS1	ENST00000673630.1		c.-15-179G>T		intron	N/A	ENSP00000501073.1	P31327-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000227 AC: 3 AN: 1322458 Hom.: 0 Cov.: 26 AF XY: 0.00000308 AC XY: 2 AN XY: 648922

African (AFR) AF: 0.00 AC: 0 AN: 29290

American (AMR) AF: 0.00 AC: 0 AN: 28568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21266

East Asian (EAS) AF: 0.0000288 AC: 1 AN: 34740

South Asian (SAS) AF: 0.00 AC: 0 AN: 68884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4924

European-Non Finnish (NFE) AF: 0.00000192 AC: 2 AN: 1043208

Other (OTH) AF: 0.00 AC: 0 AN: 54716

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		1.9
PromoterAI		-0.073	Neutral

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

Other links and lift over

dbSNP: rs6732642; hg19: chr2-211421264;