rs114819130
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BS1BS2
The NM_001875.5(CPS1):c.449G>A(p.Gly150Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0104 in 1,613,504 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G150G) has been classified as Likely benign.
Frequency
Consequence
NM_001875.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPS1 | NM_001875.5 | c.449G>A | p.Gly150Glu | missense_variant | 4/38 | ENST00000233072.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPS1 | ENST00000233072.10 | c.449G>A | p.Gly150Glu | missense_variant | 4/38 | 1 | NM_001875.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00614 AC: 933AN: 152010Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.00639 AC: 1605AN: 251346Hom.: 4 AF XY: 0.00635 AC XY: 863AN XY: 135840
GnomAD4 exome AF: 0.0108 AC: 15828AN: 1461376Hom.: 114 Cov.: 31 AF XY: 0.0107 AC XY: 7780AN XY: 727006
GnomAD4 genome ? AF: 0.00613 AC: 933AN: 152128Hom.: 4 Cov.: 32 AF XY: 0.00565 AC XY: 420AN XY: 74350
ClinVar
Submissions by phenotype
Congenital hyperammonemia, type I Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 10, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 15, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | CPS1: BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2021 | This variant is associated with the following publications: (PMID: 18666241) - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 09, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
CPS1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 12, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at