X-48523553-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006579.3(EBP):c.-73-146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (0 hom., 0 hem., cov: 9)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: EBP NM_006579.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.872

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant X-48523553-G-A is Benign according to our data. Variant chrX-48523553-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1190152.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBP	NM_006579.3	c.-73-146G>A		intron_variant		ENST00000495186.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBP	ENST00000495186.6	c.-73-146G>A		intron_variant		1	NM_006579.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 266 AN: 46019 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 8697 FAILED QC

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.0144

Gnomad AMR AF: 0.00758

Gnomad ASJ AF: 0.00219

Gnomad EAS AF: 0.00161

Gnomad SAS AF: 0.00114

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0139

Gnomad NFE AF: 0.00488

Gnomad OTH AF: 0.00914

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 225437 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 71905

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00578 AC: 266 AN: 46025 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 8703

Gnomad4 AFR AF: 0.00449

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00219

Gnomad4 EAS AF: 0.00161

Gnomad4 SAS AF: 0.00115

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.00488

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00350 Hom.: 0

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

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.88
Dann	Benign	0.33

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: rs1380692589; hg19: chrX-48381941;