X-48523711-CTTTTTTTTTT-CTTTT

Variant names:

• chrX-48523711-CTTTTTT-C
• rs782299900
• NM_006579.3:c.-48_-43delTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006579.3(EBP):​c.-48_-43delTTTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 860,247 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000011 (0 hom., 1 hem., cov: 0)
  • Exomes 𝑓: 0.000028 (0 hom. 2 hem.)
• Consequence: EBP NM_006579.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• 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: Likely_benign. The variant received -4 ACMG points.

• 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.-48_-43delTTTTTT		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.-48_-43delTTTTTT		5_prime_UTR	Exon 2 of 5	ENSP00000417052.1	Q15125
	ENSG00000286268	ENST00000651615.1		c.-48_-43delTTTTTT		5_prime_UTR	Exon 2 of 7	ENSP00000498524.1	A0A494C0F3
	EBP	ENST00000882075.1		c.-48_-43delTTTTTT		5_prime_UTR	Exon 3 of 6	ENSP00000552134.1

Frequencies

GnomAD3 genomes AF: 0.0000114 AC: 1 AN: 87650 Hom.: 0 Cov.: 0

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: 0.000557

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000285 AC: 22 AN: 772597 Hom.: 0 AF XY: 0.00000885 AC XY: 2 AN XY: 225917

⚠️ 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: 18216

American (AMR) AF: 0.00 AC: 0 AN: 19994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15661

East Asian (EAS) AF: 0.00 AC: 0 AN: 24399

South Asian (SAS) AF: 0.000232 AC: 9 AN: 38866

European-Finnish (FIN) AF: 0.0000321 AC: 1 AN: 31139

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2292

European-Non Finnish (NFE) AF: 0.0000187 AC: 11 AN: 587656

Other (OTH) AF: 0.0000291 AC: 1 AN: 34374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000166867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000114 AC: 1 AN: 87650 Hom.: 0 Cov.: 0 AF XY: 0.0000512 AC XY: 1 AN XY: 19548

African (AFR) AF: 0.00 AC: 0 AN: 23809

American (AMR) AF: 0.00 AC: 0 AN: 7471

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 2762

South Asian (SAS) AF: 0.000557 AC: 1 AN: 1795

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 45051

Other (OTH) AF: 0.00 AC: 0 AN: 1156

Alfa AF: 0.00 Hom.: 352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.53

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;