dbSNP rs72614119: OCRL:n.91+218C>T (chrX-129540157-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.180

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
OCRL	NM_000276.4 link	c.-283C>T	upstream_gene_variant	ENST00000371113.9	NP_000267.2	Q01968-1
OCRL	NM_001318784.2 link	c.-283C>T	upstream_gene_variant		NP_001305713.1	Q504W7
OCRL	NM_001587.4 link	c.-283C>T	upstream_gene_variant		NP_001578.2	Q01968-2A0A2X0TVZ9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
OCRL	ENST00000486673.1 link	n.91+218C>T	intron_variant	Intron 1 of 7	5
OCRL	ENST00000371113.9 link	c.-283C>T	upstream_gene_variant		1	NM_000276.4	ENSP00000360154.4	Q01968-1
OCRL	ENST00000357121.5 link	c.-283C>T	upstream_gene_variant		1		ENSP00000349635.5	Q01968-2
OCRL	ENST00000691455.1 link	n.-283C>T	upstream_gene_variant				ENSP00000510265.1	A0A8I5KYX7

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

7073

AN:

111710

Hom.:

358

Cov.:

AF XY:

0.0636

AC XY:

2157

AN XY:

33940

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.0950

Gnomad4 ASJ exome

AF:

0.0211

Gnomad4 EAS exome

AF:

0.329

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.0149

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.0540

GnomAD4 genome

AF:

0.0633

AC:

7075

AN:

111747

Hom.:

357

Cov.:

AF XY:

0.0637

AC XY:

2164

AN XY:

33987

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.0770

Gnomad4 ASJ

AF:

0.0215

Gnomad4 EAS

AF:

0.333

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.0149

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.0585

Alfa

AF:

0.0339

Hom.:

214

Bravo

AF:

0.0761

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.91

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over