X-48523553-GAAAAA-GA

Variant names:

• chrX-48523553-GAAAA-G
• rs782437115
• NM_006579.3:c.-73-132_-73-129delAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006579.3(EBP):​c.-73-132_-73-129delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 225,215 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.00013 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: EBP NM_006579.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.-73-132_-73-129delAAAA		intron	N/A	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.-73-132_-73-129delAAAA		intron	N/A	ENSP00000417052.1	Q15125
	ENSG00000286268	ENST00000651615.1		c.-73-132_-73-129delAAAA		intron	N/A	ENSP00000498524.1	A0A494C0F3
	EBP	ENST00000882083.1		c.-205_-202delAAAA		5_prime_UTR	Exon 1 of 4	ENSP00000552142.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 46570 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000129 AC: 29 AN: 225215 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 71791

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6736

American (AMR) AF: 0.0000926 AC: 1 AN: 10795

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6085

East Asian (EAS) AF: 0.0000790 AC: 1 AN: 12661

South Asian (SAS) AF: 0.00 AC: 0 AN: 23656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12171

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 831

European-Non Finnish (NFE) AF: 0.000172 AC: 24 AN: 139479

Other (OTH) AF: 0.000234 AC: 3 AN: 12801

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 46570 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 8906

African (AFR) AF: 0.00 AC: 0 AN: 12152

American (AMR) AF: 0.00 AC: 0 AN: 3459

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1378

East Asian (EAS) AF: 0.00 AC: 0 AN: 1259

South Asian (SAS) AF: 0.00 AC: 0 AN: 881

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1149

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 72

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 25312

Other (OTH) AF: 0.00 AC: 0 AN: 553

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23

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: rs782437115; hg19: chrX-48381941;