chr2-210556728-A-ATCT
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1
The ENST00000430249.7(CPS1):c.15_16insTTC(p.Ile5_Lys6insPhe) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,610,000 control chromosomes in the GnomAD database, including 135,416 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I5I) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000430249.7 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPS1 | NM_001875.5 | c.-4_-3insTTC | 5_prime_UTR_variant | 1/38 | ENST00000233072.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPS1 | ENST00000233072.10 | c.-4_-3insTTC | 5_prime_UTR_variant | 1/38 | 1 | NM_001875.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.462 AC: 70024AN: 151426Hom.: 16788 Cov.: 0
GnomAD3 exomes AF: 0.438 AC: 109431AN: 250072Hom.: 24596 AF XY: 0.435 AC XY: 58779AN XY: 135168
GnomAD4 exome AF: 0.399 AC: 581701AN: 1458456Hom.: 118572 Cov.: 32 AF XY: 0.401 AC XY: 291067AN XY: 725582
GnomAD4 genome AF: 0.463 AC: 70144AN: 151544Hom.: 16844 Cov.: 0 AF XY: 0.466 AC XY: 34513AN XY: 74056
ClinVar
Submissions by phenotype
Congenital hyperammonemia, type I Benign:5
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | May 31, 2017 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Likely benign, no assertion criteria provided | curation | SingHealth Duke-NUS Institute of Precision Medicine | Jun 07, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, flagged submission | clinical testing | GeneDx | Mar 13, 2014 | The variant is found in UCD-MET panel(s). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2Other:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 14, 2017 | Variant summary: The CPS1 c.-4_-3insTTC variant (also known as c.15_16insTTC based upon NM_001122633.2) involves the alteration of a 5' UTR nucleotide that 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant will not affect ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 52532/120770 control chromosomes (11669 homozygotes) at a frequency of 0.4349756, which is approximately 275 times the estimated maximal expected allele frequency of a pathogenic CPS1 variant (0.0015811). Therefore, suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely benign/benign." Taken together, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 06, 2021 | - - |
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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at