X-48523786-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. A5A) has been classified as Likely 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

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

chondrodysplasia punctata 2, X-linked dominant
Inheritance: XL Classification: DEFINITIVE Submitted by: Illumina
MEND syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
X-linked chondrodysplasia punctata 2
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

EBP links:

ENSG00000286268 (HGNC:):

ENSG00000286268 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006579.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBP	NM_006579.3	MANE Select	c.15G>T	p.Ala5Ala	synonymous	Exon 2 of 5	NP_006570.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EBP	ENST00000495186.6	TSL:1 MANE Select	c.15G>T	p.Ala5Ala	synonymous	Exon 2 of 5	ENSP00000417052.1
ENSG00000286268	ENST00000651615.1		c.15G>T	p.Ala5Ala	synonymous	Exon 2 of 7	ENSP00000498524.1
EBP	ENST00000882073.1		c.15G>T	p.Ala5Ala	synonymous	Exon 3 of 6	ENSP00000552132.1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

29826

AN:

102490

Hom.:

3798

Cov.:

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

GnomAD2 exomes

AF:

0.330

AC:

56135

AN:

170094

AF XY:

0.325

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 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

African (AFR)

AF:

0.193

AC:

5078

AN:

26326

American (AMR)

AF:

0.345

AC:

11874

AN:

34457

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

3679

AN:

19260

East Asian (EAS)

AF:

0.437

AC:

13119

AN:

30025

South Asian (SAS)

AF:

0.301

AC:

16165

AN:

53769

European-Finnish (FIN)

AF:

0.406

AC:

16330

AN:

40228

Middle Eastern (MID)

AF:

0.176

AC:

716

AN:

4074

European-Non Finnish (NFE)

AF:

0.348

AC:

291896

AN:

838903

Other (OTH)

AF:

0.312

AC:

14305

AN:

45877

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

9269

18538

27806

37075

46344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10142

20284

30426

40568

50710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.291

AC:

29837

AN:

102523

Hom.:

3804

Cov.:

AF XY:

0.262

AC XY:

6833

AN XY:

26065

show subpopulations

African (AFR)

AF:

0.189

AC:

5286

AN:

27943

American (AMR)

AF:

0.309

AC:

2874

AN:

9288

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

502

AN:

2549

East Asian (EAS)

AF:

0.388

AC:

1241

AN:

3199

South Asian (SAS)

AF:

0.282

AC:

618

AN:

2190

European-Finnish (FIN)

AF:

0.369

AC:

1707

AN:

4624

Middle Eastern (MID)

AF:

0.154

AC:

AN:

201

European-Non Finnish (NFE)

AF:

0.337

AC:

17029

AN:

50509

Other (OTH)

AF:

0.267

AC:

369

AN:

1384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

734

1468

2203

2937

3671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.303

Hom.:

13898

Bravo

AF:

0.290

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Chondrodysplasia punctata 2 X-linked dominant (1)

MEND syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.66

PhyloP100

-0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over