rs587783620

Variant names:

• chrX-48528445-CAAG-C
• rs587783620
• NM_006579.3:c.687_689delGAA

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_006579.3(EBP):​c.687_689delGAA​(p.Lys229del) variant causes a disruptive 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 (★★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000013 (0 hom. 2 hem.)
• Consequence: EBP NM_006579.3 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.68
• Publications: 0 publications found

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]

EBP Gene-Disease associations (from GenCC):

• chondrodysplasia punctata 2, X-linked dominant

  Inheritance: XL Classification: DEFINITIVE Submitted by: Illumina
• MEND syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, ClinGen
• X-linked chondrodysplasia punctata 2

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ENSG00000286268 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006579.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBP	NM_006579.3	MANE Select	c.687_689delGAA	p.Lys229del	disruptive_inframe_deletion	Exon 5 of 5	NP_006570.1	Q15125

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBP	ENST00000495186.6	TSL:1 MANE Select	c.687_689delGAA	p.Lys229del	disruptive_inframe_deletion	Exon 5 of 5	ENSP00000417052.1	Q15125
	ENSG00000286268	ENST00000651615.1		c.469+1166_469+1168delGAA		intron	N/A	ENSP00000498524.1	A0A494C0F3
	EBP	ENST00000882073.1		c.687_689delGAA	p.Lys229del	disruptive_inframe_deletion	Exon 6 of 6	ENSP00000552132.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.0000133 AC: 14 AN: 1053616 Hom.: 0 AF XY: 0.00000582 AC XY: 2 AN XY: 343770

African (AFR) AF: 0.00 AC: 0 AN: 24921

American (AMR) AF: 0.00 AC: 0 AN: 28047

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18649

East Asian (EAS) AF: 0.00 AC: 0 AN: 27216

South Asian (SAS) AF: 0.00 AC: 0 AN: 49893

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3723

European-Non Finnish (NFE) AF: 0.0000159 AC: 13 AN: 819450

Other (OTH) AF: 0.0000225 AC: 1 AN: 44379

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Chondrodysplasia punctata 2 X-linked dominant (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587783620; hg19: chrX-48386833;