rs587784230

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

pseudo-TORCH syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
pseudo-TORCH syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

OCLN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCLN	NM_001205254.2 link	c.70C>G	p.Pro24Ala	missense_variant	Exon 3 of 9	ENST00000396442.7	NP_001192183.1	Q16625-1A8K3T2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCLN	ENST00000396442.7 link	c.70C>G	p.Pro24Ala	missense_variant	Exon 3 of 9	1	NM_001205254.2	ENSP00000379719.2		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

GnomAD2 exomes

AF:

0.00881

AC:

2214

AN:

251396

AF XY:

0.00832

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 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

African (AFR)

AF:

0.00158

AC:

AN:

33478

American (AMR)

AF:

0.00760

AC:

340

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00601

AC:

157

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00210

AC:

181

AN:

86250

European-Finnish (FIN)

AF:

0.0213

AC:

1140

AN:

53398

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0118

AC:

13065

AN:

1111750

Other (OTH)

AF:

0.00801

AC:

484

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

753

1507

2260

3014

3767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00842

AC:

1283

AN:

152306

Hom.:

Cov.:

AF XY:

0.00850

AC XY:

633

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

41550

American (AMR)

AF:

0.0100

AC:

153

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00165

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0169

AC:

179

AN:

10608

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0123

AC:

835

AN:

68034

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

150

225

300

375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

OCLN: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Dec 15, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Nov 05, 2015

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pseudo-TORCH syndrome 1

Benign:1

Jul 08, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

4.8

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

Mutation Taster

=83/17

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over