X-48523711-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006579.3(EBP):c.-44_-43dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (239 hom., 813 hem., cov: 0)
  • Exomes 𝑓: 0.012 (4 hom. 52 hem.)
• Consequence: EBP NM_006579.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.474

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 Benign. Variant got -10 ACMG points.

• BP6: Variant X-48523711-C-CTT is Benign according to our data. Variant chrX-48523711-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1273004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBP	NM_006579.3	c.-44_-43dup		5_prime_UTR_variant	2/5	ENST00000495186.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBP	ENST00000495186.6	c.-44_-43dup		5_prime_UTR_variant	2/5	1	NM_006579.3	P1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 5486 AN: 87598 Hom.: 240 Cov.: 0 AF XY: 0.0416 AC XY: 813 AN XY: 19538

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.00644

Gnomad MID AF: 0.0319

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0760

GnomAD4 exome AF: 0.0121 AC: 9164 AN: 757619 Hom.: 4 Cov.: 0 AF XY: 0.000242 AC XY: 52 AN XY: 214951

Gnomad4 AFR exome AF: 0.0331

Gnomad4 AMR exome AF: 0.00758

Gnomad4 ASJ exome AF: 0.00866

Gnomad4 EAS exome AF: 0.0164

Gnomad4 SAS exome AF: 0.0118

Gnomad4 FIN exome AF: 0.00457

Gnomad4 NFE exome AF: 0.0119

Gnomad4 OTH exome AF: 0.0125

GnomAD4 genome AF: 0.0627 AC: 5487 AN: 87573 Hom.: 239 Cov.: 0 AF XY: 0.0416 AC XY: 813 AN XY: 19545

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0417

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.0757

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.00644

Gnomad4 NFE AF: 0.0423

Gnomad4 OTH AF: 0.0780

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 23, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs782299900; hg19: chrX-48382099;