rs147125035

Positions:

chr5-69509160-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001205254.2(OCLN):c.70C>G(p.Pro24Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0104 in 1,613,900 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 9 hom., cov: 33)

Exomes 𝑓: 0.011 ( 91 hom. )

Consequence

OCLN
NM_001205254.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.78

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0089428425).

BP6

Variant 5-69509160-C-G is Benign according to our data. Variant chr5-69509160-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 159462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00842 (1283/152306) while in subpopulation NFE AF= 0.0123 (835/68034). AF 95% confidence interval is 0.0116. There are 9 homozygotes in gnomad4. There are 633 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCLN	NM_001205254.2 linkuse as main transcript	c.70C>G	p.Pro24Ala	missense_variant	3/9	ENST00000396442.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCLN	ENST00000396442.7 linkuse as main transcript	c.70C>G	p.Pro24Ala	missense_variant	3/9	1	NM_001205254.2	P1	Q16625-1

Frequencies

GnomAD3 genomes

AF:

0.00843

AC:

1283

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00881

AC:

2214

AN:

251396

Hom.:

AF XY:

0.00832

AC XY:

1131

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00703

Gnomad ASJ exome

AF:

0.00625

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.0106

AC:

15434

AN:

1461594

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

7386

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.00760

Gnomad4 ASJ exome

AF:

0.00601

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00210

Gnomad4 FIN exome

AF:

0.0213

Gnomad4 NFE exome

AF:

0.0118

Gnomad4 OTH exome

AF:

0.00801

GnomAD4 genome

AF:

0.00842

AC:

1283

AN:

152306

Hom.:

Cov.:

AF XY:

0.00850

AC XY:

633

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00165

Gnomad4 FIN

AF:

0.0169

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00707

TwinsUK

AF:

0.0124

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0102

AC:

ExAC

AF:

0.00853

AC:

1036

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00943

EpiControl

AF:

0.00972

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	OCLN: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 15, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 05, 2015	- -

Pseudo-TORCH syndrome 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

.;T

MetaRNN

Benign

0.0089

T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.7

D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

0.99

D;D

Vest4

0.57

MVP

0.94

MPC

0.36

ClinPred

0.014

GERP RS

6.0

Varity_R

0.10

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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