rs61733458
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000096.4(CP):c.1652C>T(p.Thr551Ile) variant causes a missense change. The variant allele was found at a frequency of 0.031 in 1,612,482 control chromosomes in the GnomAD database, including 978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_000096.4 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CP | NM_000096.4 | c.1652C>T | p.Thr551Ile | missense_variant | 9/19 | ENST00000264613.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CP | ENST00000264613.11 | c.1652C>T | p.Thr551Ile | missense_variant | 9/19 | 1 | NM_000096.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0227 AC: 3460AN: 152130Hom.: 66 Cov.: 32
GnomAD3 exomes AF: 0.0285 AC: 7148AN: 251032Hom.: 142 AF XY: 0.0311 AC XY: 4223AN XY: 135704
GnomAD4 exome AF: 0.0319 AC: 46572AN: 1460234Hom.: 913 Cov.: 30 AF XY: 0.0330 AC XY: 23995AN XY: 726518
GnomAD4 genome ? AF: 0.0227 AC: 3456AN: 152248Hom.: 65 Cov.: 32 AF XY: 0.0227 AC XY: 1691AN XY: 74452
ClinVar
Submissions by phenotype
Deficiency of ferroxidase Pathogenic:1Benign:6
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | GenePathDx, GenePath diagnostics | Feb 01, 2017 | 25 years old, suspected case of Aceruloplasminemia. Next generation DNA sequencing ofperipheral blood sample has revealed the presence of two homozygous variants in the CP gene. The c.1652C>T variant is being classified as a ‘Variant of Unknown Significance, likely benign’, while the c.1679G>T variant is being classified as a ‘Variant of Unknown Significance, likely pathogenic’ based on available evidence in the databases and in silico mutation prediction methods. - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 12, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Pathogenic, flagged submission | curation | GeneReviews | Apr 18, 2013 | - - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 16, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at