X-48523711-CTTTTTTTTTT-CTTTTTTTTT

Variant names:

• chrX-48523711-CT-C
• rs782299900
• NM_006579.3:c.-43delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006579.3(EBP):​c.-43delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (0 hom., 30 hem., cov: 0)
  • Exomes 𝑓: 0.18 (3 hom. 48 hem.)
• Consequence: EBP NM_006579.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant X-48523711-CT-C is Benign according to our data. Variant chrX-48523711-CT-C is described in ClinVar as Benign. ClinVar VariationId is 516179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00376 (329/87604) while in subpopulation AFR AF = 0.00705 (168/23829). AF 95% confidence interval is 0.00618. There are 0 homozygotes in GnomAd4. There are 30 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 30 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.-43delT		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.-43delT		5_prime_UTR	Exon 2 of 5	ENSP00000417052.1	Q15125
	ENSG00000286268	ENST00000651615.1		c.-43delT		5_prime_UTR	Exon 2 of 7	ENSP00000498524.1	A0A494C0F3
	EBP	ENST00000882075.1		c.-43delT		5_prime_UTR	Exon 3 of 6	ENSP00000552134.1

Frequencies

GnomAD3 genomes AF: 0.00372 AC: 326 AN: 87629 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00697

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00201

Gnomad ASJ AF: 0.000859

Gnomad EAS AF: 0.00217

Gnomad SAS AF: 0.00223

Gnomad FIN AF: 0.00967

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.00519

GnomAD4 exome AF: 0.180 AC: 119250 AN: 661077 Hom.: 3 Cov.: 0 AF XY: 0.000369 AC XY: 48 AN XY: 130125

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

African (AFR) AF: 0.189 AC: 2981 AN: 15804

American (AMR) AF: 0.172 AC: 2949 AN: 17156

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 2256 AN: 13082

East Asian (EAS) AF: 0.179 AC: 3615 AN: 20247

South Asian (SAS) AF: 0.105 AC: 3149 AN: 29954

European-Finnish (FIN) AF: 0.149 AC: 4038 AN: 27152

Middle Eastern (MID) AF: 0.138 AC: 261 AN: 1890

European-Non Finnish (NFE) AF: 0.187 AC: 94450 AN: 506345

Other (OTH) AF: 0.189 AC: 5551 AN: 29447

⚠️ 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: 0.00376 AC: 329 AN: 87604 Hom.: 0 Cov.: 0 AF XY: 0.00154 AC XY: 30 AN XY: 19540

African (AFR) AF: 0.00705 AC: 168 AN: 23829

American (AMR) AF: 0.00214 AC: 16 AN: 7474

Ashkenazi Jewish (ASJ) AF: 0.000859 AC: 2 AN: 2327

East Asian (EAS) AF: 0.00218 AC: 6 AN: 2752

South Asian (SAS) AF: 0.00226 AC: 4 AN: 1773

European-Finnish (FIN) AF: 0.00967 AC: 24 AN: 2481

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

European-Non Finnish (NFE) AF: 0.00229 AC: 103 AN: 45034

Other (OTH) AF: 0.00515 AC: 6 AN: 1164

Alfa AF: 0.000400 Hom.: 352

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

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: rs782299900; hg19: chrX-48382099;