chrX-48523711-C-CTTTTT

Variant names:

• chrX-48523711-C-CTTTTT
• rs782299900
• NM_006579.3:c.-47_-43dupTTTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006579.3(EBP):​c.-47_-43dupTTTTT 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
• Publications: 2 publications found

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

ENSG00000286268 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 XL gene

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.-47_-43dupTTTTT		5_prime_UTR	Exon 2 of 5	NP_006570.1	Q15125

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBP	ENST00000495186.6	TSL:1 MANE Select	c.-47_-43dupTTTTT		5_prime_UTR	Exon 2 of 5	ENSP00000417052.1	Q15125
	ENSG00000286268	ENST00000651615.1		c.-47_-43dupTTTTT		5_prime_UTR	Exon 2 of 7	ENSP00000498524.1	A0A494C0F3
	EBP	ENST00000882075.1		c.-47_-43dupTTTTT		5_prime_UTR	Exon 3 of 6	ENSP00000552134.1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 1587 AN: 87610 Hom.: 21 Cov.: 0

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

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

African (AFR) AF: 0.000549 AC: 10 AN: 18209

American (AMR) AF: 0.00161 AC: 32 AN: 19927

Ashkenazi Jewish (ASJ) AF: 0.00575 AC: 89 AN: 15490

East Asian (EAS) AF: 0.0000410 AC: 1 AN: 24400

South Asian (SAS) AF: 0.00498 AC: 191 AN: 38375

European-Finnish (FIN) AF: 0.00145 AC: 45 AN: 31060

Middle Eastern (MID) AF: 0.00760 AC: 17 AN: 2238

European-Non Finnish (NFE) AF: 0.00322 AC: 1882 AN: 584893

Other (OTH) AF: 0.00383 AC: 131 AN: 34176

⚠️ 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.

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

African (AFR) AF: 0.00306 AC: 73 AN: 23828

American (AMR) AF: 0.0108 AC: 81 AN: 7476

Ashkenazi Jewish (ASJ) AF: 0.0503 AC: 117 AN: 2325

East Asian (EAS) AF: 0.00 AC: 0 AN: 2752

South Asian (SAS) AF: 0.0198 AC: 35 AN: 1771

European-Finnish (FIN) AF: 0.00322 AC: 8 AN: 2487

Middle Eastern (MID) AF: 0.0926 AC: 15 AN: 162

European-Non Finnish (NFE) AF: 0.0274 AC: 1232 AN: 45017

Other (OTH) AF: 0.0198 AC: 23 AN: 1163

Alfa AF: 0.00248 Hom.: 352

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.47
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs782299900; hg19: chrX-48382099;