dbSNP rs10906310: OPTN:c.1613-48C>A (chr10-13136697-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001008212.2(OPTN):c.1613-48C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,610,842 control chromosomes in the GnomAD database, including 50,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4886 hom., cov: 32)

Exomes 𝑓: 0.25 ( 45912 hom. )

Consequence

OPTN
NM_001008212.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.246

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=-0.86).

BP6

Variant 10-13136697-C-A is Benign according to our data. Variant chr10-13136697-C-A is described in ClinVar as [Benign]. Clinvar id is 256879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2 link	c.1613-48C>A	intron_variant	Intron 14 of 14	ENST00000378747.8	NP_001008213.1	Q96CV9-1
OPTN	NM_001008211.1 link	c.1613-48C>A	intron_variant	Intron 15 of 15		NP_001008212.1	Q96CV9-1
OPTN	NM_001008213.1 link	c.1613-48C>A	intron_variant	Intron 15 of 15		NP_001008214.1	Q96CV9-1
OPTN	NM_021980.4 link	c.1613-48C>A	intron_variant	Intron 13 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.1613-48C>A		intron_variant	Intron 14 of 14	1	NM_001008212.2	ENSP00000368021.3		Q96CV9-1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38428

AN:

151808

Hom.:

4882

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.220

GnomAD3 exomes

AF:

0.262

AC:

65023

AN:

247764

Hom.:

8875

AF XY:

0.266

AC XY:

35671

AN XY:

134118

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.335

Gnomad SAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.246

AC:

358170

AN:

1458918

Hom.:

45912

Cov.:

AF XY:

0.249

AC XY:

180511

AN XY:

725736

show subpopulations

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.217

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.387

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.315

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.253

AC:

38456

AN:

151924

Hom.:

4886

Cov.:

AF XY:

0.255

AC XY:

18967

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.263

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.231

Gnomad4 EAS

AF:

0.341

Gnomad4 SAS

AF:

0.347

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.246

Hom.:

2972

Bravo

AF:

0.242

Asia WGS

AF:

0.331

AC:

1150

AN:

3478

ClinVar

Significance: 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: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.86

CADD

Benign

3.8

DANN

Benign

0.40

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