rs369518478

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.922G>A(p.Val308Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V308L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 11)

Exomes 𝑓: 0.0012 ( 31 hom. )

Failed GnomAD Quality Control

Consequence

OCLN
NM_001205254.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.87

Publications

6 publications found

Variant links:

COSMIC-nc: COSV62285774

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=0.0031420588).

BP6

Variant 5-69534724-G-A is Benign according to our data. Variant chr5-69534724-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 377038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.0012 (993/828788) while in subpopulation AFR AF = 0.0198 (347/17482). AF 95% confidence interval is 0.0181. There are 31 homozygotes in GnomAdExome4. There are 624 alleles in the male GnomAdExome4 subpopulation. Median coverage is 12. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OCLN	NM_001205254.2 link	c.922G>A	p.Val308Met	missense_variant	Exon 5 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.922G>A	p.Val308Met	missense_variant	Exon 5 of 9	1	NM_001205254.2	ENSP00000379719.2		Q16625-1

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

383

AN:

93456

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.000761

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00350

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000183

Gnomad OTH

AF:

0.00781

GnomAD2 exomes

AF:

0.00220

AC:

500

AN:

226864

AF XY:

0.00231

show subpopulations

Gnomad AFR exome

AF:

0.0216

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.000344

Gnomad EAS exome

AF:

0.0000559

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00120

AC:

993

AN:

828788

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

624

AN XY:

431272

show subpopulations

African (AFR)

AF:

0.0198

AC:

347

AN:

17482

American (AMR)

AF:

0.00120

AC:

AN:

40928

Ashkenazi Jewish (ASJ)

AF:

0.000241

AC:

AN:

20708

East Asian (EAS)

AF:

0.0000823

AC:

AN:

36436

South Asian (SAS)

AF:

0.00618

AC:

436

AN:

70550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51060

Middle Eastern (MID)

AF:

0.00317

AC:

AN:

3150

European-Non Finnish (NFE)

AF:

0.000111

AC:

AN:

549860

Other (OTH)

AF:

0.00212

AC:

AN:

38614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

109

145

181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00413

AC:

386

AN:

93528

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

173

AN XY:

43362

show subpopulations

African (AFR)

AF:

0.0179

AC:

348

AN:

19468

American (AMR)

AF:

0.00124

AC:

AN:

8870

Ashkenazi Jewish (ASJ)

AF:

0.000761

AC:

AN:

2628

East Asian (EAS)

AF:

0.00

AC:

AN:

3528

South Asian (SAS)

AF:

0.00305

AC:

AN:

2292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.000183

AC:

AN:

49048

Other (OTH)

AF:

0.00767

AC:

AN:

1174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000540

Hom.:

ExAC

AF:

0.00308

AC:

365

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 12, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 20, 2016

GeneDx

Significance:Likely 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.069

T;T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.67

.;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.32

N;N;.

PhyloP100

1.9

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.18

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.61

T;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.18

MVP

0.59

MPC

1.9

ClinPred

0.0024

GERP RS

1.8

Varity_R

0.035

gMVP

0.27

Mutation Taster

=96/4

polymorphism (auto)

(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