NM_006579.3:c.-43dupT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006579.3(EBP):​c.-43dupT 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 0.27 (3327 hom., 3551 hem., cov: 0)
  • Exomes 𝑓: 0.094 (37 hom. 156 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-C-CT is Benign according to our data. Variant chrX-48523711-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1229850.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.269 AC: 23545 AN: 87616 Hom.: 3322 Cov.: 0

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.0943 AC: 66831 AN: 708781 Hom.: 37 Cov.: 0 AF XY: 0.000925 AC XY: 156 AN XY: 168695

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

African (AFR) AF: 0.0695 AC: 1188 AN: 17104

American (AMR) AF: 0.0751 AC: 1370 AN: 18251

Ashkenazi Jewish (ASJ) AF: 0.0445 AC: 657 AN: 14769

East Asian (EAS) AF: 0.121 AC: 2582 AN: 21404

South Asian (SAS) AF: 0.0560 AC: 1856 AN: 33142

European-Finnish (FIN) AF: 0.0700 AC: 2012 AN: 28750

Middle Eastern (MID) AF: 0.0439 AC: 94 AN: 2142

European-Non Finnish (NFE) AF: 0.100 AC: 54302 AN: 541468

Other (OTH) AF: 0.0872 AC: 2770 AN: 31751

⚠️ 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: 0.269 AC: 23551 AN: 87591 Hom.: 3327 Cov.: 0 AF XY: 0.182 AC XY: 3551 AN XY: 19529

African (AFR) AF: 0.169 AC: 4035 AN: 23821

American (AMR) AF: 0.265 AC: 1979 AN: 7478

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 475 AN: 2327

East Asian (EAS) AF: 0.347 AC: 955 AN: 2752

South Asian (SAS) AF: 0.239 AC: 424 AN: 1775

European-Finnish (FIN) AF: 0.211 AC: 525 AN: 2486

Middle Eastern (MID) AF: 0.114 AC: 19 AN: 166

European-Non Finnish (NFE) AF: 0.326 AC: 14693 AN: 45018

Other (OTH) AF: 0.242 AC: 282 AN: 1164

Alfa AF: 0.0797 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)		0.060		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;