X-48523711-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006579.3(EBP):c.-43dup 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBP	NM_006579.3	c.-43dup		5_prime_UTR_variant	2/5	ENST00000495186.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBP	ENST00000495186.6	c.-43dup		5_prime_UTR_variant	2/5	1	NM_006579.3	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 23545 AN: 87616 Hom.: 3322 Cov.: 0 AF XY: 0.182 AC XY: 3552 AN XY: 19522

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

Gnomad4 AFR exome AF: 0.0695

Gnomad4 AMR exome AF: 0.0751

Gnomad4 ASJ exome AF: 0.0445

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.0560

Gnomad4 FIN exome AF: 0.0700

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.0872

GnomAD4 genome AF: 0.269 AC: 23551 AN: 87591 Hom.: 3327 Cov.: 0 AF XY: 0.182 AC XY: 3551 AN XY: 19529

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.242

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2020

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs782299900; hg19: chrX-48382099;