rs3048

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000495186.6(EBP):c.15G>A(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,195,834 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A5A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., 1 hem., cov: 19)

Exomes 𝑓: 0.000010 ( 0 hom. 4 hem. )

Consequence

EBP
ENST00000495186.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-48523786-G-A is Benign according to our data. Variant chrX-48523786-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1520959.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

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

BS2

High Hemizygotes in GnomAdExome4 at 4 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000495186.6. 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>A	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>A	p.Ala5Ala	synonymous	Exon 2 of 5	ENSP00000417052.1
ENSG00000286268	ENST00000651615.1		c.15G>A	p.Ala5Ala	synonymous	Exon 2 of 7	ENSP00000498524.1
EBP	ENST00000446158.5	TSL:5	c.15G>A	p.Ala5Ala	synonymous	Exon 3 of 6	ENSP00000390031.1

Frequencies

GnomAD3 genomes

AF:

0.0000195

AC:

AN:

102586

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000396

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000176

AC:

AN:

170094

AF XY:

0.0000176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000383

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1093215

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

359469

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26328

American (AMR)

AF:

0.0000290

AC:

AN:

34500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19263

East Asian (EAS)

AF:

0.00

AC:

AN:

30033

South Asian (SAS)

AF:

0.00

AC:

AN:

53780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40241

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4074

European-Non Finnish (NFE)

AF:

0.0000119

AC:

AN:

839108

Other (OTH)

AF:

0.00

AC:

AN:

45888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.0000195

AC:

AN:

102619

Hom.:

Cov.:

AF XY:

0.0000384

AC XY:

AN XY:

26075

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27977

American (AMR)

AF:

0.00

AC:

AN:

9307

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2549

East Asian (EAS)

AF:

0.00

AC:

AN:

3200

South Asian (SAS)

AF:

0.00

AC:

AN:

2190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4627

Middle Eastern (MID)

AF:

0.00

AC:

AN:

201

European-Non Finnish (NFE)

AF:

0.0000396

AC:

AN:

50546

Other (OTH)

AF:

0.00

AC:

AN:

1386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

13898

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.7

(source)

DANN

Benign

0.72

PhyloP100

-0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=93/7

polymorphism

(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

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

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over