X-48523711-CTTTTTTTTTT-CTTTTTTTTTTTTT

Variant names:

• chrX-48523711-C-CTTT
• rs782299900
• NM_006579.3:c.-45_-43dupTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_006579.3(EBP):​c.-45_-43dupTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00043 (1 hom., 6 hem., cov: 0)
  • Exomes 𝑓: 0.0015 (0 hom. 36 hem.)
• Consequence: EBP NM_006579.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000434 (38/87620) while in subpopulation EAS AF = 0.00255 (7/2750). AF 95% confidence interval is 0.00119. There are 1 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 6 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.-45_-43dupTTT		5_prime_UTR	Exon 2 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.-45_-43dupTTT		5_prime_UTR	Exon 2 of 5	ENSP00000417052.1	Q15125
	ENSG00000286268	ENST00000651615.1		c.-45_-43dupTTT		5_prime_UTR	Exon 2 of 7	ENSP00000498524.1	A0A494C0F3
	EBP	ENST00000882075.1		c.-45_-43dupTTT		5_prime_UTR	Exon 3 of 6	ENSP00000552134.1

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 38 AN: 87645 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000882

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000803

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00254

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000888

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00150 AC: 1152 AN: 769068 Hom.: 0 Cov.: 0 AF XY: 0.000161 AC XY: 36 AN XY: 223658

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

African (AFR) AF: 0.00121 AC: 22 AN: 18165

American (AMR) AF: 0.00105 AC: 21 AN: 19940

Ashkenazi Jewish (ASJ) AF: 0.00225 AC: 35 AN: 15535

East Asian (EAS) AF: 0.000905 AC: 22 AN: 24296

South Asian (SAS) AF: 0.00175 AC: 67 AN: 38373

European-Finnish (FIN) AF: 0.000612 AC: 19 AN: 31070

Middle Eastern (MID) AF: 0.00487 AC: 11 AN: 2259

European-Non Finnish (NFE) AF: 0.00155 AC: 906 AN: 585251

Other (OTH) AF: 0.00143 AC: 49 AN: 34179

⚠️ 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 AF: 0.000434 AC: 38 AN: 87620 Hom.: 1 Cov.: 0 AF XY: 0.000307 AC XY: 6 AN XY: 19552

African (AFR) AF: 0.000881 AC: 21 AN: 23826

American (AMR) AF: 0.000802 AC: 6 AN: 7480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2327

East Asian (EAS) AF: 0.00255 AC: 7 AN: 2750

South Asian (SAS) AF: 0.00 AC: 0 AN: 1775

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2487

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.0000888 AC: 4 AN: 45040

Other (OTH) AF: 0.00 AC: 0 AN: 1165

Alfa AF: 0.00 Hom.: 352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.47
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs782299900; hg19: chrX-48382099;