2-210630863-C-T

Position:

• chr2-210630863-C-T

Variant summary

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

The NM_001875.5(CPS1):​c.2688-6839C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,850 control chromosomes in the GnomAD database, including 7,750 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 0.31 (7750 hom., cov: 32)
• Consequence: CPS1 NM_001875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350

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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPS1	NM_001875.5	c.2688-6839C>T		intron_variant		ENST00000233072.10	NP_001866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPS1	ENST00000233072.10	c.2688-6839C>T		intron_variant		1	NM_001875.5	ENSP00000233072.5

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46649 AN: 151734 Hom.: 7751 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.307 AC: 46672 AN: 151850 Hom.: 7750 Cov.: 32 AF XY: 0.308 AC XY: 22852 AN XY: 74166

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.330

Alfa AF: 0.365 Hom.: 13706

Bravo AF: 0.291

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.1
DANN	Benign	0.79

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: rs12468557; hg19: chr2-211495587;