rs2234968

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001008212.2(OPTN):c.102G>A(p.Thr34Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,613,578 control chromosomes in the GnomAD database, including 53,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3653 hom., cov: 30)

Exomes 𝑓: 0.26 ( 49586 hom. )

Consequence

OPTN
NM_001008212.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -3.19

Variant links:

Genes affected

OPTN (HGNC:17142): (optineurin) This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

OPTN links:

OPTN (HGNC:):

OPTN 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=-0.79).

BP6

Variant 10-13109224-G-A is Benign according to our data. Variant chr10-13109224-G-A is described in ClinVar as [Benign]. Clinvar id is 96022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-13109224-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPTN	NM_001008212.2 linkuse as main transcript	c.102G>A	p.Thr34Thr	synonymous_variant	3/15	ENST00000378747.8	NP_001008213.1	Q96CV9-1
OPTN	NM_001008211.1 linkuse as main transcript	c.102G>A	p.Thr34Thr	synonymous_variant	4/16		NP_001008212.1	Q96CV9-1
OPTN	NM_001008213.1 linkuse as main transcript	c.102G>A	p.Thr34Thr	synonymous_variant	4/16		NP_001008214.1	Q96CV9-1
OPTN	NM_021980.4 linkuse as main transcript	c.102G>A	p.Thr34Thr	synonymous_variant	2/14		NP_068815.2	Q96CV9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8 linkuse as main transcript	c.102G>A	p.Thr34Thr	synonymous_variant	3/15	1	NM_001008212.2	ENSP00000368021.3		Q96CV9-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30209

AN:

151882

Hom.:

3651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0535

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.235

GnomAD3 exomes

AF:

0.242

AC:

60876

AN:

251260

Hom.:

7960

AF XY:

0.244

AC XY:

33116

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.0479

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.202

Gnomad SAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.256

AC:

374781

AN:

1461578

Hom.:

49586

Cov.:

AF XY:

0.256

AC XY:

186429

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.0443

Gnomad4 AMR exome

AF:

0.278

Gnomad4 ASJ exome

AF:

0.329

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.221

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.199

AC:

30209

AN:

152000

Hom.:

3653

Cov.:

AF XY:

0.197

AC XY:

14651

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0533

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.269

Gnomad4 OTH

AF:

0.237

Alfa

AF:

0.258

Hom.:

10767

Bravo

AF:

0.199

Asia WGS

AF:

0.210

AC:

731

AN:

3478

EpiCase

AF:

0.284

EpiControl

AF:

0.283

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 21, 2017	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 10, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 19172505, 17122126, 28993189, 31198474, 17361544) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Amyotrophic lateral sclerosis type 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Primary open angle glaucoma;C1842026:Glaucoma 1, open angle, E;C3150692:Amyotrophic lateral sclerosis type 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Primary open angle glaucoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.70

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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