rs587783620
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PM4_SupportingBS2
The NM_006579.3(EBP):βc.687_689delβ(p.Lys229del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000133 in 1,053,616 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: not found (cov: 22)
Exomes π: 0.000013 ( 0 hom. 2 hem. )
Consequence
EBP
NM_006579.3 inframe_deletion
NM_006579.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.68
Genes affected
EBP (HGNC:3133): (EBP cholestenol delta-isomerase) The protein encoded by this gene is an integral membrane protein of the endoplasmic reticulum. It is a high affinity binding protein for the antiischemic phenylalkylamine Ca2+ antagonist [3H]emopamil and the photoaffinity label [3H]azidopamil. It is similar to sigma receptors and may be a member of a superfamily of high affinity drug-binding proteins in the endoplasmic reticulum of different tissues. This protein shares structural features with bacterial and eukaryontic drug transporting proteins. It has four putative transmembrane segments and contains two conserved glutamate residues which may be involved in the transport of cationic amphiphilics. Another prominent feature of this protein is its high content of aromatic amino acid residues (>23%) in its transmembrane segments. These aromatic amino acid residues have been suggested to be involved in the drug transport by the P-glycoprotein. Mutations in this gene cause Chondrodysplasia punctata 2 (CDPX2; also known as Conradi-Hunermann syndrome). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM1
?
In a chain 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase (size 228) in uniprot entity EBP_HUMAN there are 35 pathogenic changes around while only 14 benign (71%) in NM_006579.3
PM4
?
Nonframeshift variant in NON repetitive region in NM_006579.3. Strenght limited to Supporting due to length of the change: 1aa.
BS2
?
High Hemizygotes in GnomAdExome4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EBP | NM_006579.3 | c.687_689del | p.Lys229del | inframe_deletion | 5/5 | ENST00000495186.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EBP | ENST00000495186.6 | c.687_689del | p.Lys229del | inframe_deletion | 5/5 | 1 | NM_006579.3 | P1 | |
EBP | ENST00000276096.10 | n.645_647del | non_coding_transcript_exon_variant | 5/5 | 2 | ||||
EBP | ENST00000498425.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome AF: 0.0000133 AC: 14AN: 1053616Hom.: 0 AF XY: 0.00000582 AC XY: 2AN XY: 343770
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GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
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22
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 158554). This variant has not been reported in the literature in individuals affected with EBP-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.687_689del, results in the deletion of 1 amino acid(s) of the EBP protein (p.Lys229del), but otherwise preserves the integrity of the reading frame. - |
Chondrodysplasia punctata 2 X-linked dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at