2-210608346-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
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
Consequence
NM_001875.5 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CPS1 | NM_001875.5 | c.2193-15G>T | intron_variant | Intron 18 of 37 | ENST00000233072.10 | NP_001866.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.102 AC: 15515AN: 151782Hom.: 996 Cov.: 32
GnomAD3 exomes AF: 0.127 AC: 31517AN: 249112Hom.: 2250 AF XY: 0.127 AC XY: 17155AN XY: 134794
GnomAD4 exome AF: 0.125 AC: 182204AN: 1456356Hom.: 12439 Cov.: 31 AF XY: 0.126 AC XY: 91408AN XY: 724766
GnomAD4 genome AF: 0.102 AC: 15515AN: 151900Hom.: 999 Cov.: 32 AF XY: 0.104 AC XY: 7741AN XY: 74220
ClinVar
Submissions by phenotype
not specified Benign:4
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Congenital hyperammonemia, type I Benign:4
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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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:2
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Variant summary: c. c.2193-15G>T in CPS1 gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this do not affect a normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.1255 (14937 / 119028 chrs tested), across multiple ethnicities, including numerous homozygous occurrences. The observed frequencies exceed the maximum expected allele frequency for a pathogenic variant of 0.0015%, suggesting that it is a benign polymorphism. The variant of interest has been reported as Benign by several reputable databases/clinical laboratory. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at