X-48523730-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.342

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 1191185.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBP	NM_006579.3	c.-42A>T		5_prime_UTR_variant	2/5	ENST00000495186.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBP	ENST00000495186.6	c.-42A>T		5_prime_UTR_variant	2/5	1	NM_006579.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 38 AN: 46940 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 12960 FAILED QC

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

GnomAD3 exomes AF: 0.00792 AC: 398 AN: 50230 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16462

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 SAS exome AF: 0.00919

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.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 246320

Gnomad4 AFR exome AF: 0.000472

Gnomad4 AMR exome AF: 0.00209

Gnomad4 ASJ exome AF: 0.00371

Gnomad4 EAS exome AF: 0.0000833

Gnomad4 SAS exome AF: 0.00207

Gnomad4 FIN exome AF: 0.00242

Gnomad4 NFE exome AF: 0.000221

Gnomad4 OTH exome AF: 0.000484

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000810 AC: 38 AN: 46921 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 12979

Gnomad4 AFR AF: 0.000231

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000857

Gnomad4 FIN AF: 0.00316

Gnomad4 NFE AF: 0.00106

Gnomad4 OTH AF: 0.00163

Alfa AF: 0.000169 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	6.4
Dann	Benign	0.26
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

LitVar

Other links and lift over

dbSNP: rs782032695; hg19: chrX-48382118;