NM_006579.3:c.-44_-43dupTT

Variant names:

• chrX-48523711-C-CTT
• rs782299900
• NM_006579.3:c.-44_-43dupTT

Variant summary

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

The NM_006579.3(EBP):​c.-44_-43dupTT 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 0.063 (239 hom., 813 hem., cov: 0)
  • Exomes 𝑓: 0.012 (4 hom. 52 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-CTT is Benign according to our data. Variant chrX-48523711-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 1273004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 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.-44_-43dupTT		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.-44_-43dupTT		5_prime_UTR	Exon 2 of 5	ENSP00000417052.1	Q15125
	ENSG00000286268	ENST00000651615.1		c.-44_-43dupTT		5_prime_UTR	Exon 2 of 7	ENSP00000498524.1	A0A494C0F3
	EBP	ENST00000882075.1		c.-44_-43dupTT		5_prime_UTR	Exon 3 of 6	ENSP00000552134.1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 5486 AN: 87598 Hom.: 240 Cov.: 0

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.00644

Gnomad MID AF: 0.0319

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0760

GnomAD4 exome AF: 0.0121 AC: 9164 AN: 757619 Hom.: 4 Cov.: 0 AF XY: 0.000242 AC XY: 52 AN XY: 214951

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

African (AFR) AF: 0.0331 AC: 581 AN: 17568

American (AMR) AF: 0.00758 AC: 149 AN: 19646

Ashkenazi Jewish (ASJ) AF: 0.00866 AC: 133 AN: 15355

East Asian (EAS) AF: 0.0164 AC: 388 AN: 23627

South Asian (SAS) AF: 0.0118 AC: 439 AN: 37075

European-Finnish (FIN) AF: 0.00457 AC: 141 AN: 30821

Middle Eastern (MID) AF: 0.0157 AC: 35 AN: 2225

European-Non Finnish (NFE) AF: 0.0119 AC: 6878 AN: 577647

Other (OTH) AF: 0.0125 AC: 420 AN: 33655

⚠️ 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: 0.0627 AC: 5487 AN: 87573 Hom.: 239 Cov.: 0 AF XY: 0.0416 AC XY: 813 AN XY: 19545

African (AFR) AF: 0.115 AC: 2735 AN: 23805

American (AMR) AF: 0.0417 AC: 312 AN: 7478

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 92 AN: 2327

East Asian (EAS) AF: 0.0757 AC: 208 AN: 2747

South Asian (SAS) AF: 0.0648 AC: 115 AN: 1775

European-Finnish (FIN) AF: 0.00644 AC: 16 AN: 2486

Middle Eastern (MID) AF: 0.0361 AC: 6 AN: 166

European-Non Finnish (NFE) AF: 0.0423 AC: 1904 AN: 45018

Other (OTH) AF: 0.0780 AC: 91 AN: 1167

Alfa AF: 0.00776 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

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

Other links and lift over

dbSNP: rs782299900; hg19: chrX-48382099;