ENST00000486673.1:n.91+237C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

OCRL Gene-Disease associations (from GenCC):

• Dent disease type 2

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• oculocerebrorenal syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000486673.1. 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
	OCRL	NM_000276.4	MANE Select	c.-264C>T		upstream_gene	N/A	NP_000267.2
	OCRL	NM_001318784.2		c.-264C>T		upstream_gene	N/A	NP_001305713.1
	OCRL	NM_001587.4		c.-264C>T		upstream_gene	N/A	NP_001578.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OCRL	ENST00000486673.1	TSL:5	n.91+237C>T		intron	N/A
	OCRL	ENST00000371113.9	TSL:1 MANE Select	c.-264C>T		upstream_gene	N/A	ENSP00000360154.4	Q01968-1
	OCRL	ENST00000357121.5	TSL:1	c.-264C>T		upstream_gene	N/A	ENSP00000349635.5	Q01968-2

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 7862 AN: 111861 Hom.: 444 Cov.: 22

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

African (AFR) AF: 0.153 AC: 1225 AN: 8002

American (AMR) AF: 0.0959 AC: 1265 AN: 13197

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 177 AN: 8774

East Asian (EAS) AF: 0.322 AC: 6506 AN: 20181

South Asian (SAS) AF: 0.134 AC: 3541 AN: 26403

European-Finnish (FIN) AF: 0.0144 AC: 283 AN: 19591

Middle Eastern (MID) AF: 0.0498 AC: 62 AN: 1245

European-Non Finnish (NFE) AF: 0.0121 AC: 2177 AN: 179374

Other (OTH) AF: 0.0555 AC: 988 AN: 17812

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

African (AFR) AF: 0.149 AC: 4590 AN: 30705

American (AMR) AF: 0.0815 AC: 873 AN: 10707

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 55 AN: 2658

East Asian (EAS) AF: 0.334 AC: 1155 AN: 3463

South Asian (SAS) AF: 0.137 AC: 371 AN: 2702

European-Finnish (FIN) AF: 0.0147 AC: 89 AN: 6062

Middle Eastern (MID) AF: 0.0143 AC: 3 AN: 210

European-Non Finnish (NFE) AF: 0.0118 AC: 627 AN: 53173

Other (OTH) AF: 0.0663 AC: 102 AN: 1539

Alfa AF: 0.0442 Hom.: 212

Bravo AF: 0.0849

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		-0.47
PromoterAI		-0.054	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7057639; hg19: chrX-128674153;