10-13116364-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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:4

Conservation

PhyloP100: -1.17

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

glaucoma, normal tension, susceptibility to
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
amyotrophic lateral sclerosis type 12
Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
glaucoma 1, open angle, E
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

OPTN 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 (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 VariationId 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	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2 link	c.626+24G>A	intron_variant	Intron 6 of 14	ENST00000378747.8	NP_001008213.1	Q96CV9-1
OPTN	NM_001008211.1 link	c.626+24G>A	intron_variant	Intron 7 of 15		NP_001008212.1	Q96CV9-1
OPTN	NM_001008213.1 link	c.626+24G>A	intron_variant	Intron 7 of 15		NP_001008214.1	Q96CV9-1
OPTN	NM_021980.4 link	c.626+24G>A	intron_variant	Intron 5 of 13		NP_068815.2	Q96CV9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8 link	c.626+24G>A		intron_variant	Intron 6 of 14	1	NM_001008212.2	ENSP00000368021.3		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

GnomAD2 exomes

AF:

0.0251

AC:

6274

AN:

250110

AF XY:

0.0234

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 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

African (AFR)

AF:

0.0817

AC:

2695

AN:

32998

American (AMR)

AF:

0.0475

AC:

2120

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00135

AC:

AN:

25970

East Asian (EAS)

AF:

0.0957

AC:

3785

AN:

39544

South Asian (SAS)

AF:

0.0539

AC:

4622

AN:

85752

European-Finnish (FIN)

AF:

0.000619

AC:

AN:

53306

Middle Eastern (MID)

AF:

0.0112

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00451

AC:

4907

AN:

1087804

Other (OTH)

AF:

0.0210

AC:

1246

AN:

59446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

922

1843

2765

3686

4608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.0324

AC:

4932

AN:

152274

Hom.:

170

Cov.:

AF XY:

0.0328

AC XY:

2442

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0823

AC:

3420

AN:

41550

American (AMR)

AF:

0.0318

AC:

486

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.0701

AC:

362

AN:

5164

South Asian (SAS)

AF:

0.0567

AC:

273

AN:

4816

European-Finnish (FIN)

AF:

0.000470

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00457

AC:

311

AN:

68028

Other (OTH)

AF:

0.0321

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

221

442

662

883

1104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0187

Hom.:

Bravo

AF:

0.0352

Asia WGS

AF:

0.0830

AC:

287

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Dec 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.17

(source)

DANN

Benign

0.57

PhyloP100

-1.2

PromoterAI

-0.0042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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