ENST00000486673.1:n.91+218C>T

Variant names:

• chrX-129540157-C-T
• rs72614119
• ENST00000486673.1:n.91+218C>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+218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 388,745 control chromosomes in the GnomAD database, including 1,381 homozygotes. There are 7,536 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (357 hom., 2164 hem., cov: 22)
  • Exomes 𝑓: 0.055 (1024 hom. 5372 hem.)
• Consequence: OCRL ENST00000486673.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.180
• Publications: 2 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=-0.61).
• BP6: Variant X-129540157-C-T is Benign according to our data. Variant chrX-129540157-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 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.-283C>T		upstream_gene	N/A	NP_000267.2
	OCRL	NM_001318784.2		c.-283C>T		upstream_gene	N/A	NP_001305713.1
	OCRL	NM_001587.4		c.-283C>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+218C>T		intron	N/A
	OCRL	ENST00000371113.9	TSL:1 MANE Select	c.-283C>T		upstream_gene	N/A	ENSP00000360154.4	Q01968-1
	OCRL	ENST00000357121.5	TSL:1	c.-283C>T		upstream_gene	N/A	ENSP00000349635.5	Q01968-2

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 7073 AN: 111710 Hom.: 358 Cov.: 22

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.0215

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.0216

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0586

GnomAD4 exome AF: 0.0554 AC: 15341 AN: 276998 Hom.: 1024 AF XY: 0.0627 AC XY: 5372 AN XY: 85644

African (AFR) AF: 0.132 AC: 991 AN: 7487

American (AMR) AF: 0.0950 AC: 1174 AN: 12358

Ashkenazi Jewish (ASJ) AF: 0.0211 AC: 172 AN: 8171

East Asian (EAS) AF: 0.329 AC: 6203 AN: 18878

South Asian (SAS) AF: 0.136 AC: 3498 AN: 25710

European-Finnish (FIN) AF: 0.0149 AC: 271 AN: 18170

Middle Eastern (MID) AF: 0.0509 AC: 58 AN: 1140

European-Non Finnish (NFE) AF: 0.0123 AC: 2066 AN: 168282

Other (OTH) AF: 0.0540 AC: 908 AN: 16802

GnomAD4 genome AF: 0.0633 AC: 7075 AN: 111747 Hom.: 357 Cov.: 22 AF XY: 0.0637 AC XY: 2164 AN XY: 33987

African (AFR) AF: 0.126 AC: 3873 AN: 30718

American (AMR) AF: 0.0770 AC: 822 AN: 10670

Ashkenazi Jewish (ASJ) AF: 0.0215 AC: 57 AN: 2653

East Asian (EAS) AF: 0.333 AC: 1149 AN: 3447

South Asian (SAS) AF: 0.138 AC: 369 AN: 2683

European-Finnish (FIN) AF: 0.0149 AC: 90 AN: 6025

Middle Eastern (MID) AF: 0.0144 AC: 3 AN: 209

European-Non Finnish (NFE) AF: 0.0117 AC: 622 AN: 53127

Other (OTH) AF: 0.0585 AC: 90 AN: 1538

Alfa AF: 0.0339 Hom.: 214

Bravo AF: 0.0761

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	-0.61
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		-0.18
PromoterAI		-0.24	Neutral

Splicing

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

Other links and lift over

dbSNP: rs72614119; hg19: chrX-128674134;