chrX-129540176-C-T

Variant names:

• chrX-129540176-C-T
• rs7057639
• ENST00000486673.1:n.91+237C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000486673.1(OCRL):​n.91+237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 406,477 control chromosomes in the GnomAD database, including 1,525 homozygotes. There are 8,082 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (443 hom., 2381 hem., cov: 22)
  • Exomes 𝑓: 0.055 (1082 hom. 5701 hem.)
• Consequence: OCRL ENST00000486673.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.471

Genes affected

OCRL (HGNC:8108): (OCRL inositol polyphosphate-5-phosphatase) This gene encodes an inositol polyphosphate 5-phosphatase. This protein is involved in regulating membrane trafficking and is located in numerous subcellular locations including the trans-Golgi network, clathrin-coated vesicles and, endosomes and the plasma membrane. This protein may also play a role in primary cilium formation. Mutations in this gene cause oculocerebrorenal syndrome of Lowe and also Dent disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant X-129540176-C-T is Benign according to our data. Variant chrX-129540176-C-T is described in ClinVar as [Benign]. Clinvar id is 1259336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCRL	NM_000276.4	c.-264C>T		upstream_gene_variant		ENST00000371113.9	NP_000267.2
OCRL	NM_001318784.2	c.-264C>T		upstream_gene_variant			NP_001305713.1
OCRL	NM_001587.4	c.-264C>T		upstream_gene_variant			NP_001578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCRL	ENST00000486673.1	n.91+237C>T		intron_variant	Intron 1 of 7	5
OCRL	ENST00000371113.9	c.-264C>T		upstream_gene_variant		1	NM_000276.4	ENSP00000360154.4
OCRL	ENST00000357121.5	c.-264C>T		upstream_gene_variant		1		ENSP00000349635.5
OCRL	ENST00000691455.1	n.-264C>T		upstream_gene_variant				ENSP00000510265.1

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 7862 AN: 111861 Hom.: 444 Cov.: 22 AF XY: 0.0697 AC XY: 2373 AN XY: 34069

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.0216

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.0664

GnomAD4 exome AF: 0.0551 AC: 16224 AN: 294579 Hom.: 1082 AF XY: 0.0601 AC XY: 5701 AN XY: 94875

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.0959

Gnomad4 ASJ exome AF: 0.0202

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0144

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.0555

GnomAD4 genome AF: 0.0703 AC: 7865 AN: 111898 Hom.: 443 Cov.: 22 AF XY: 0.0698 AC XY: 2381 AN XY: 34116

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0815

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.0663

Alfa AF: 0.0442 Hom.: 212

Bravo AF: 0.0849

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7057639; hg19: chrX-128674153;