chrX-48523786-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006579.3(EBP):c.15G>T(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,195,442 control chromosomes in the GnomAD database, including 47,684 homozygotes. There are 128,731 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 3804 hom., 6833 hem., cov: 19)

Exomes 𝑓: 0.34 ( 43880 hom. 121898 hem. )

Consequence

EBP
NM_006579.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.544

Variant links:

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 links:

ENSG00000286268 (HGNC:):

ENSG00000286268 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-48523786-G-T is Benign according to our data. Variant chrX-48523786-G-T is described in ClinVar as [Benign]. Clinvar id is 158531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.544 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBP	NM_006579.3 link	c.15G>T	p.Ala5Ala	synonymous_variant	Exon 2 of 5	ENST00000495186.6	NP_006570.1	Q15125A0A024QYX0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBP	ENST00000495186.6 link	c.15G>T	p.Ala5Ala	synonymous_variant	Exon 2 of 5	1	NM_006579.3	ENSP00000417052.1		Q15125
ENSG00000286268	ENST00000651615.1 link	c.15G>T	p.Ala5Ala	synonymous_variant	Exon 2 of 7			ENSP00000498524.1		A0A494C0F3

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

29826

AN:

102490

Hom.:

3798

Cov.:

AF XY:

0.263

AC XY:

6832

AN XY:

26020

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.330

AC:

56135

AN:

170094

Hom.:

6532

AF XY:

0.325

AC XY:

18447

AN XY:

56688

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.346

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.413

Gnomad SAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.407

Gnomad NFE exome

AF:

0.339

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.341

AC:

373162

AN:

1092919

Hom.:

43880

Cov.:

AF XY:

0.339

AC XY:

121898

AN XY:

359315

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.345

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.437

Gnomad4 SAS exome

AF:

0.301

Gnomad4 FIN exome

AF:

0.406

Gnomad4 NFE exome

AF:

0.348

Gnomad4 OTH exome

AF:

0.312

GnomAD4 genome

AF:

0.291

AC:

29837

AN:

102523

Hom.:

3804

Cov.:

AF XY:

0.262

AC XY:

6833

AN XY:

26065

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.309

Gnomad4 ASJ

AF:

0.197

Gnomad4 EAS

AF:

0.388

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.303

Hom.:

9860

Bravo

AF:

0.290

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 29, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Chondrodysplasia punctata 2 X-linked dominant

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MEND syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over