rs12415716

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001008212.2(OPTN):c.*1421T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 178,626 control chromosomes in the GnomAD database, including 5,391 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4496 hom., cov: 33)

Exomes 𝑓: 0.25 ( 895 hom. )

Consequence

OPTN
NM_001008212.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.339

Publications

13 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2 link	c.*1421T>G	3_prime_UTR_variant	Exon 15 of 15	ENST00000378747.8	NP_001008213.1	Q96CV9-1
OPTN	NM_001008211.1 link	c.*1421T>G	downstream_gene_variant			NP_001008212.1	Q96CV9-1
OPTN	NM_001008213.1 link	c.*1421T>G	downstream_gene_variant			NP_001008214.1	Q96CV9-1
OPTN	NM_021980.4 link	c.*1421T>G	downstream_gene_variant			NP_068815.2	Q96CV9-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
OPTN	ENST00000378747.8 link	c.*1421T>G	3_prime_UTR_variant	Exon 15 of 15	1	NM_001008212.2	ENSP00000368021.3	Q96CV9-1
OPTN	ENST00000378748.7 link	c.*1421T>G	3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000368022.3	Q96CV9-1
OPTN	ENST00000378757.6 link	c.*1421T>G	3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000368032.2	Q96CV9-1
OPTN	ENST00000378752.7 link	c.*1421T>G	3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000368027.3	Q96CV9-2

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34970

AN:

152074

Hom.:

4502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.0980

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.401

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.267

GnomAD4 exome

AF:

0.248

AC:

6554

AN:

26434

Hom.:

895

Cov.:

AF XY:

0.250

AC XY:

3030

AN XY:

12110

show subpopulations

African (AFR)

AF:

0.148

AC:

130

AN:

880

American (AMR)

AF:

0.251

AC:

142

AN:

566

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

558

AN:

1700

East Asian (EAS)

AF:

0.0882

AC:

488

AN:

5532

South Asian (SAS)

AF:

0.273

AC:

AN:

216

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AF:

0.398

AC:

AN:

176

European-Non Finnish (NFE)

AF:

0.298

AC:

4537

AN:

15224

Other (OTH)

AF:

0.267

AC:

568

AN:

2124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

207

414

622

829

1036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.230

AC:

34969

AN:

152192

Hom.:

4496

Cov.:

AF XY:

0.225

AC XY:

16727

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.137

AC:

5671

AN:

41538

American (AMR)

AF:

0.262

AC:

4004

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1214

AN:

3472

East Asian (EAS)

AF:

0.0984

AC:

511

AN:

5194

South Asian (SAS)

AF:

0.219

AC:

1058

AN:

4824

European-Finnish (FIN)

AF:

0.181

AC:

1919

AN:

10600

Middle Eastern (MID)

AF:

0.387

AC:

113

AN:

292

European-Non Finnish (NFE)

AF:

0.289

AC:

19632

AN:

67966

Other (OTH)

AF:

0.267

AC:

563

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1350

2700

4051

5401

6751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.227

Hom.:

684

Bravo

AF:

0.232

Asia WGS

AF:

0.197

AC:

686

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Amyotrophic Lateral Sclerosis, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary open angle glaucoma

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

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

-0.75

CADD

Benign

5.0

(source)

DANN

Benign

0.79

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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