rs2287600

Variant names:

• chr2-210608346-G-T
• rs2287600
• NM_001875.5:c.2193-15G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-210608346-G-T
• chr2-210608346-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001875.5(CPS1):​c.2193-15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,608,256 control chromosomes in the GnomAD database, including 13,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (999 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12439 hom.)
• Consequence: CPS1 NM_001875.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.141
• Publications: 9 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: Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-210608346-G-T is Benign according to our data. Variant chr2-210608346-G-T is described in ClinVar as Benign. ClinVar VariationId is 137023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001875.5. 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_001875.5	MANE Select	c.2193-15G>T		intron	N/A	NP_001866.2
	CPS1	NM_001369256.1		c.2226-15G>T		intron	N/A	NP_001356185.1
	CPS1	NM_001122633.3		c.2193-15G>T		intron	N/A	NP_001116105.2	P31327-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPS1	ENST00000233072.10	TSL:1 MANE Select	c.2193-15G>T		intron	N/A	ENSP00000233072.5	P31327-1
	CPS1	ENST00000430249.7	TSL:1	c.2211-15G>T		intron	N/A	ENSP00000402608.2	P31327-3
	CPS1	ENST00000451903.3	TSL:1	c.840-15G>T		intron	N/A	ENSP00000406136.2	P31327-2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15515 AN: 151782 Hom.: 996 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.127 AC: 31517 AN: 249112 AF XY: 0.127

Gnomad AFR exome AF: 0.0349

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.236

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.125 AC: 182204 AN: 1456356 Hom.: 12439 Cov.: 31 AF XY: 0.126 AC XY: 91408 AN XY: 724766

African (AFR) AF: 0.0328 AC: 1093 AN: 33286

American (AMR) AF: 0.133 AC: 5914 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3512 AN: 25980

East Asian (EAS) AF: 0.291 AC: 11513 AN: 39610

South Asian (SAS) AF: 0.132 AC: 11401 AN: 86096

European-Finnish (FIN) AF: 0.113 AC: 6016 AN: 53024

Middle Eastern (MID) AF: 0.0817 AC: 469 AN: 5744

European-Non Finnish (NFE) AF: 0.121 AC: 134445 AN: 1108004

Other (OTH) AF: 0.130 AC: 7841 AN: 60102

GnomAD4 genome AF: 0.102 AC: 15515 AN: 151900 Hom.: 999 Cov.: 32 AF XY: 0.104 AC XY: 7741 AN XY: 74220

African (AFR) AF: 0.0363 AC: 1508 AN: 41504

American (AMR) AF: 0.133 AC: 2020 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3464

East Asian (EAS) AF: 0.263 AC: 1343 AN: 5112

South Asian (SAS) AF: 0.144 AC: 694 AN: 4822

European-Finnish (FIN) AF: 0.114 AC: 1211 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 7977 AN: 67852

Other (OTH) AF: 0.106 AC: 223 AN: 2112

Alfa AF: 0.0781 Hom.: 139

Bravo AF: 0.0979

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Congenital hyperammonemia, type I (4)
-	-	4	not specified (4)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.39
PhyloP100		-0.14
Mutation Taster		=19/81	disease causing (long InDel)

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: rs2287600; hg19: chr2-211473070; COSMIC: COSV51812966; COSMIC: COSV51812966;