chrX-48523809-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 4P and 9B. PP3_StrongBP6BS1BS2

The NM_006579.3(EBP):c.38C>G(p.Pro13Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000136 in 1,205,503 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 51 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 5 hem., cov: 21)

Exomes 𝑓: 0.00014 ( 0 hom. 46 hem. )

Consequence

EBP
NM_006579.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 6.59

Publications

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

EBP links:

ENSG00000286268 (HGNC:):

ENSG00000286268 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.956

BP6

Variant X-48523809-C-G is Benign according to our data. Variant chrX-48523809-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1965021.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000129 (14/108255) while in subpopulation NFE AF = 0.00023 (12/52285). AF 95% confidence interval is 0.000132. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBP	NM_006579.3	MANE Select	c.38C>G	p.Pro13Arg	missense	Exon 2 of 5	NP_006570.1	Q15125

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EBP	ENST00000495186.6	TSL:1 MANE Select	c.38C>G	p.Pro13Arg	missense	Exon 2 of 5	ENSP00000417052.1	Q15125
ENSG00000286268	ENST00000651615.1		c.38C>G	p.Pro13Arg	missense	Exon 2 of 7	ENSP00000498524.1	A0A494C0F3
EBP	ENST00000882073.1		c.38C>G	p.Pro13Arg	missense	Exon 3 of 6	ENSP00000552132.1

Frequencies

GnomAD3 genomes

AF:

0.000129

AC:

AN:

108255

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000230

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000946

AC:

AN:

179625

AF XY:

0.0000777

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000175

Gnomad OTH exome

AF:

0.000673

GnomAD4 exome

AF:

0.000137

AC:

150

AN:

1097248

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

362648

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26386

American (AMR)

AF:

0.00

AC:

AN:

35142

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19362

East Asian (EAS)

AF:

0.00

AC:

AN:

30167

South Asian (SAS)

AF:

0.00

AC:

AN:

53949

European-Finnish (FIN)

AF:

0.0000494

AC:

AN:

40488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.000170

AC:

143

AN:

841573

Other (OTH)

AF:

0.0000651

AC:

AN:

46053

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000129

AC:

AN:

108255

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

AN XY:

30675

show subpopulations

African (AFR)

AF:

0.0000339

AC:

AN:

29537

American (AMR)

AF:

0.00

AC:

AN:

10007

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2629

East Asian (EAS)

AF:

0.00

AC:

AN:

3447

South Asian (SAS)

AF:

0.00

AC:

AN:

2434

European-Finnish (FIN)

AF:

0.000179

AC:

AN:

5583

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000230

AC:

AN:

52285

Other (OTH)

AF:

0.00

AC:

AN:

1425

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000130

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Pathogenic

0.51

BayesDel_noAF

Pathogenic

0.77

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.89

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.91

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

0.98

MutationAssessor

Pathogenic

3.4

PhyloP100

6.6

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-8.4

REVEL

Pathogenic

0.95

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.96

MVP

1.0

MPC

1.6

ClinPred

0.64

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.95

gMVP

1.0

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over