X-48523711-C-CTTTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006579.3(EBP):c.-47_-43dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (21 hom., 201 hem., cov: 0)
  • Exomes 𝑓: 0.0031 (1 hom. 34 hem.)
• Consequence: EBP NM_006579.3 5_prime_UTR
• Clinical Significance: Likely 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-CTTTTT is Benign according to our data. Variant chrX-48523711-C-CTTTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1199761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0181 (1586/87585) while in subpopulation NFE AF= 0.0274 (1232/45017). AF 95% confidence interval is 0.0261. There are 21 homozygotes in gnomad4. There are 201 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBP	NM_006579.3	c.-47_-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.-47_-43dup		5_prime_UTR_variant	2/5	1	NM_006579.3	P1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 1587 AN: 87610 Hom.: 21 Cov.: 0 AF XY: 0.0103 AC XY: 201 AN XY: 19544

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.00331

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.0503

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.00322

Gnomad MID AF: 0.0870

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0199

GnomAD4 exome AF: 0.00312 AC: 2398 AN: 768768 Hom.: 1 Cov.: 0 AF XY: 0.000152 AC XY: 34 AN XY: 223756

Gnomad4 AFR exome AF: 0.000549

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00575

Gnomad4 EAS exome AF: 0.0000410

Gnomad4 SAS exome AF: 0.00498

Gnomad4 FIN exome AF: 0.00145

Gnomad4 NFE exome AF: 0.00322

Gnomad4 OTH exome AF: 0.00383

GnomAD4 genome AF: 0.0181 AC: 1586 AN: 87585 Hom.: 21 Cov.: 0 AF XY: 0.0103 AC XY: 201 AN XY: 19551

Gnomad4 AFR AF: 0.00306

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.0503

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0198

Gnomad4 FIN AF: 0.00322

Gnomad4 NFE AF: 0.0274

Gnomad4 OTH AF: 0.0198

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

Dec 13, 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;