rs6435580
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001875.5(CPS1):c.3756+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,378,736 control chromosomes in the GnomAD database, including 69,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.25 ( 5678 hom., cov: 32)
Exomes 𝑓: 0.31 ( 63789 hom. )
Consequence
CPS1
NM_001875.5 intron
NM_001875.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0550
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 2-210658733-C-T is Benign according to our data. Variant chr2-210658733-C-T is described in ClinVar as [Benign]. Clinvar id is 258482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPS1 | NM_001875.5 | c.3756+45C>T | intron_variant | ENST00000233072.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPS1 | ENST00000233072.10 | c.3756+45C>T | intron_variant | 1 | NM_001875.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.250 AC: 37933AN: 151986Hom.: 5683 Cov.: 32
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GnomAD3 exomes AF: 0.282 AC: 69653AN: 247160Hom.: 10943 AF XY: 0.294 AC XY: 39345AN XY: 133662
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GnomAD4 exome AF: 0.312 AC: 383221AN: 1226632Hom.: 63789 Cov.: 16 AF XY: 0.316 AC XY: 196578AN XY: 622484
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GnomAD4 genome ? AF: 0.249 AC: 37931AN: 152104Hom.: 5678 Cov.: 32 AF XY: 0.252 AC XY: 18752AN XY: 74336
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ClinVar
Significance: Benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Congenital hyperammonemia, type I Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at