Variant 5-69509789-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001205254.2(OCLN):c.699G>A(p.Leu233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 1,613,784 control chromosomes in the GnomAD database, including 1,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 63 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1103 hom. )

Consequence

OCLN
NM_001205254.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.28

Variant links:

Genes affected

OCLN (HGNC:8104): (occludin) This gene encodes an integral membrane protein that is required for cytokine-induced regulation of the tight junction paracellular permeability barrier. Mutations in this gene are thought to be a cause of band-like calcification with simplified gyration and polymicrogyria (BLC-PMG), an autosomal recessive neurologic disorder that is also known as pseudo-TORCH syndrome. Alternative splicing results in multiple transcript variants. A related pseudogene is present 1.5 Mb downstream on the q arm of chromosome 5. [provided by RefSeq, Apr 2011]

OCLN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-69509789-G-A is Benign according to our data. Variant chr5-69509789-G-A is described in ClinVar as [Benign]. Clinvar id is 138568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-69509789-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.026 (3957/152210) while in subpopulation NFE AF= 0.0382 (2598/68008). AF 95% confidence interval is 0.037. There are 63 homozygotes in gnomad4. There are 1930 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 63 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCLN	NM_001205254.2 linkuse as main transcript	c.699G>A	p.Leu233=	synonymous_variant	3/9	ENST00000396442.7	NP_001192183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCLN	ENST00000396442.7 linkuse as main transcript	c.699G>A	p.Leu233=	synonymous_variant	3/9	1	NM_001205254.2	ENSP00000379719	P1	Q16625-1

Frequencies

GnomAD3 genomes

AF:

0.0260

AC:

3958

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00681

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0463

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0382

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0233

AC:

5823

AN:

250322

Hom.:

AF XY:

0.0227

AC XY:

3070

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.00665

Gnomad AMR exome

AF:

0.0158

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00565

Gnomad FIN exome

AF:

0.0395

Gnomad NFE exome

AF:

0.0342

Gnomad OTH exome

AF:

0.0279

GnomAD4 exome

AF:

0.0356

AC:

51967

AN:

1461574

Hom.:

1103

Cov.:

AF XY:

0.0345

AC XY:

25119

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.00570

Gnomad4 AMR exome

AF:

0.0155

Gnomad4 ASJ exome

AF:

0.0125

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00565

Gnomad4 FIN exome

AF:

0.0398

Gnomad4 NFE exome

AF:

0.0414

Gnomad4 OTH exome

AF:

0.0334

GnomAD4 genome

AF:

0.0260

AC:

3957

AN:

152210

Hom.:

Cov.:

AF XY:

0.0259

AC XY:

1930

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00679

Gnomad4 AMR

AF:

0.0240

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.0463

Gnomad4 NFE

AF:

0.0382

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0316

Hom.:

Bravo

AF:

0.0246

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0330

EpiControl

AF:

0.0347

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 18, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 30, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.3

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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