Variant rs11258211 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001008212.2(OPTN):c.626+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,587,480 control chromosomes in the GnomAD database, including 803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 170 hom., cov: 32)

Exomes 𝑓: 0.014 ( 633 hom. )

Consequence

OPTN
NM_001008212.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.17

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:

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 (BayesDel_noAF=-0.84).

BP6

Variant 10-13116364-G-A is Benign according to our data. Variant chr10-13116364-G-A is described in ClinVar as [Benign]. Clinvar id is 256883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.08 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
OPTN	NM_001008212.2 linkuse as main transcript	c.626+24G>A	intron_variant	ENST00000378747.8
OPTN	NM_001008211.1 linkuse as main transcript	c.626+24G>A	intron_variant
OPTN	NM_001008213.1 linkuse as main transcript	c.626+24G>A	intron_variant
OPTN	NM_021980.4 linkuse as main transcript	c.626+24G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTN	ENST00000378747.8 linkuse as main transcript	c.626+24G>A		intron_variant		1	NM_001008212.2	P3	Q96CV9-1

Frequencies

GnomAD3 genomes

AF:

0.0322

AC:

4900

AN:

152156

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0819

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0703

Gnomad SAS

AF:

0.0566

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00457

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0251

AC:

6274

AN:

250110

Hom.:

180

AF XY:

0.0234

AC XY:

3171

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.0833

Gnomad AMR exome

AF:

0.0512

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.0563

Gnomad SAS exome

AF:

0.0531

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00362

Gnomad OTH exome

AF:

0.0141

GnomAD4 exome

AF:

0.0136

AC:

19507

AN:

1435206

Hom.:

633

Cov.:

AF XY:

0.0142

AC XY:

10181

AN XY:

715624

show subpopulations

Gnomad4 AFR exome

AF:

0.0817

Gnomad4 AMR exome

AF:

0.0475

Gnomad4 ASJ exome

AF:

0.00135

Gnomad4 EAS exome

AF:

0.0957

Gnomad4 SAS exome

AF:

0.0539

Gnomad4 FIN exome

AF:

0.000619

Gnomad4 NFE exome

AF:

0.00451

Gnomad4 OTH exome

AF:

0.0210

GnomAD4 genome

AF:

0.0324

AC:

4932

AN:

152274

Hom.:

170

Cov.:

AF XY:

0.0328

AC XY:

2442

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0823

Gnomad4 AMR

AF:

0.0318

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0701

Gnomad4 SAS

AF:

0.0567

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00457

Gnomad4 OTH

AF:

0.0321

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0352

Asia WGS

AF:

0.0830

AC:

287

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2018

This variant is associated with the following publications: (PMID: 12939304) -

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

Invitae

Jan 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.17

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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