X-48523553-G-GA

Variant summary

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

The NM_006579.3(EBP):c.-73-129dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 220,936 control chromosomes in the GnomAD database, including 63 homozygotes. There are 310 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (55 hom., 254 hem., cov: 19)
  • Exomes 𝑓: 0.28 (8 hom. 56 hem.)
• Consequence: EBP NM_006579.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.234

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-48523553-G-GA is Benign according to our data. Variant chrX-48523553-G-GA is described in ClinVar as [Benign]. Clinvar id is 1293795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.071 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBP	NM_006579.3	c.-73-129dup		intron_variant		ENST00000495186.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBP	ENST00000495186.6	c.-73-129dup		intron_variant		1	NM_006579.3	P1

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 2493 AN: 46256 Hom.: 55 Cov.: 19 AF XY: 0.0287 AC XY: 254 AN XY: 8850

Gnomad AFR AF: 0.00869

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0556

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.0642

GnomAD4 exome AF: 0.283 AC: 49368 AN: 174674 Hom.: 8 AF XY: 0.00209 AC XY: 56 AN XY: 26822

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.0539 AC: 2492 AN: 46262 Hom.: 55 Cov.: 19 AF XY: 0.0287 AC XY: 254 AN XY: 8856

Gnomad4 AFR AF: 0.00868

Gnomad4 AMR AF: 0.0340

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.0138

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.0738

Gnomad4 OTH AF: 0.0632

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

Oct 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs782437115; hg19: chrX-48381941;