rs782032695

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_006579.3(EBP):c.-42A>T variant causes a 5 prime UTR 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 0.00081 ( 0 hom., 0 hem., cov: 8)

Exomes 𝑓: 0.00049 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

EBP
NM_006579.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.342

Publications

1 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 -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-48523730-A-T is Benign according to our data. Variant chrX-48523730-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1191185.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-42A>T		5_prime_UTR	Exon 2 of 5	NP_006570.1	Q15125

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EBP	ENST00000495186.6	TSL:1 MANE Select	c.-42A>T	5_prime_UTR	Exon 2 of 5	ENSP00000417052.1	Q15125
ENSG00000286268	ENST00000651615.1		c.-42A>T	5_prime_UTR	Exon 2 of 7	ENSP00000498524.1	A0A494C0F3
EBP	ENST00000882075.1		c.-42A>T	5_prime_UTR	Exon 3 of 6	ENSP00000552134.1

Frequencies

GnomAD3 genomes

AF:

0.000810

AC:

AN:

46940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000232

Gnomad AMI

AF:

0.00317

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000849

Gnomad FIN

AF:

0.00316

Gnomad MID

AF:

0.0182

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00163

GnomAD2 exomes

AF:

0.00792

AC:

398

AN:

50230

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00232

Gnomad AMR exome

AF:

0.000763

Gnomad ASJ exome

AF:

0.0133

Gnomad EAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000485

AC:

423

AN:

871848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

246320

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000472

AC:

AN:

19050

American (AMR)

AF:

0.00209

AC:

AN:

18159

Ashkenazi Jewish (ASJ)

AF:

0.00371

AC:

AN:

15349

East Asian (EAS)

AF:

0.0000833

AC:

AN:

24018

South Asian (SAS)

AF:

0.00207

AC:

AN:

34816

European-Finnish (FIN)

AF:

0.00242

AC:

AN:

29361

Middle Eastern (MID)

AF:

0.00127

AC:

AN:

2355

European-Non Finnish (NFE)

AF:

0.000221

AC:

153

AN:

691558

Other (OTH)

AF:

0.000484

AC:

AN:

37182

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.345

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000810

AC:

AN:

46921

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

12979

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000231

AC:

AN:

12976

American (AMR)

AF:

0.00

AC:

AN:

4354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1388

East Asian (EAS)

AF:

0.00

AC:

AN:

1502

South Asian (SAS)

AF:

0.000857

AC:

AN:

1167

European-Finnish (FIN)

AF:

0.00316

AC:

AN:

1897

Middle Eastern (MID)

AF:

0.0200

AC:

AN:

100

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

22607

Other (OTH)

AF:

0.00163

AC:

AN:

615

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.313

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000169

Hom.:

ClinVar

ClinVar submissions

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

-0.87

CADD

Benign

6.4

(source)

DANN

Benign

0.26

PhyloP100

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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