rs28935174
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_006579.3(EBP):c.440G>A(p.Arg147His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R147C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006579.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EBP | NM_006579.3 | c.440G>A | p.Arg147His | missense_variant | 4/5 | ENST00000495186.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EBP | ENST00000495186.6 | c.440G>A | p.Arg147His | missense_variant | 4/5 | 1 | NM_006579.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Chondrodysplasia punctata 2 X-linked dominant Pathogenic:4
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2003 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | May 22, 2022 | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.95; 3Cnet: 0.96). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000011492). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID:10942423, 12483303, 1355069, 24726177, 7677157). Different missense changes at the same codon (p.Arg147Cys, p.Arg147Gly) have been reported to be associated with EBP related disorder (ClinVar ID: VCV000265110 / PMID: 11493318, 26075358). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 22, 2023 | Female patient witth this variant showed accumulation of 8(9)-cholesterol and 8-dehydrocholesterol by GC/MS, suggestive of a defect of sterol-delta8-isomerase, and subsequent functional studies showed that this variant partially impairs enzyme activity (Braverman et al., 1999); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11982764, 22121851, 10391219, 7677157, 1355069, 11493318, 25814754, 22229330, 12824059, 12509714, 27276700, 14632217, 12483303, 11038443, 17625999, 19416264, 31299979, 30608402, 10942423, 34450268, SunMA2023[Article]) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at