X-48523553-GA-G

Variant summary

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

The NM_006579.3(EBP):c.-73-129del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 261,050 control chromosomes in the GnomAD database, including 15 homozygotes. There are 97 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (15 hom., 95 hem., cov: 19)
  • Exomes 𝑓: 0.032 (0 hom. 2 hem.)
• Consequence: EBP NM_006579.3 intron
• Clinical Significance: Likely 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-GA-G is Benign according to our data. Variant chrX-48523553-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1212535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 1208 AN: 46545 Hom.: 15 Cov.: 19 AF XY: 0.0106 AC XY: 94 AN XY: 8897

Gnomad AFR AF: 0.0734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00454

Gnomad FIN AF: 0.00436

Gnomad MID AF: 0.0139

Gnomad NFE AF: 0.00992

Gnomad OTH AF: 0.0199

GnomAD4 exome AF: 0.0324 AC: 6948 AN: 214499 Hom.: 0 AF XY: 0.0000322 AC XY: 2 AN XY: 62119

Gnomad4 AFR exome AF: 0.0596

Gnomad4 AMR exome AF: 0.0274

Gnomad4 ASJ exome AF: 0.0295

Gnomad4 EAS exome AF: 0.0430

Gnomad4 SAS exome AF: 0.00960

Gnomad4 FIN exome AF: 0.0347

Gnomad4 NFE exome AF: 0.0336

Gnomad4 OTH exome AF: 0.0388

GnomAD4 genome AF: 0.0260 AC: 1208 AN: 46551 Hom.: 15 Cov.: 19 AF XY: 0.0107 AC XY: 95 AN XY: 8903

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00343

Gnomad4 FIN AF: 0.00436

Gnomad4 NFE AF: 0.00992

Gnomad4 OTH AF: 0.0196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 16, 2020

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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;