10-13116262-C-T

Position:

chr10-13116262-C-T

Variant summary

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

The NM_001008212.2(OPTN):c.553-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,591,242 control chromosomes in the GnomAD database, including 519,174 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 49925 hom., cov: 31)

Exomes 𝑓: 0.81 ( 469249 hom. )

Consequence

OPTN
NM_001008212.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002316

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.120

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=-0.85).

BP6

Variant 10-13116262-C-T is Benign according to our data. Variant chr10-13116262-C-T is described in ClinVar as [Benign]. Clinvar id is 197846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-13116262-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
OPTN	NM_001008212.2 linkuse as main transcript	c.553-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1 linkuse as main transcript	c.553-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001008212.1
OPTN	NM_001008213.1 linkuse as main transcript	c.553-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001008214.1
OPTN	NM_021980.4 linkuse as main transcript	c.553-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8 linkuse as main transcript	c.553-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001008212.2	ENSP00000368021	P3	Q96CV9-1

Frequencies

GnomAD3 genomes

AF:

0.809

AC:

122848

AN:

151910

Hom.:

49876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.810

Gnomad AMI

AF:

0.766

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.908

Gnomad EAS

AF:

0.741

Gnomad SAS

AF:

0.808

Gnomad FIN

AF:

0.709

Gnomad MID

AF:

0.943

Gnomad NFE

AF:

0.810

Gnomad OTH

AF:

0.849

GnomAD3 exomes

AF:

0.817

AC:

205038

AN:

251040

Hom.:

84193

AF XY:

0.817

AC XY:

110911

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.805

Gnomad AMR exome

AF:

0.880

Gnomad ASJ exome

AF:

0.917

Gnomad EAS exome

AF:

0.742

Gnomad SAS exome

AF:

0.826

Gnomad FIN exome

AF:

0.716

Gnomad NFE exome

AF:

0.818

Gnomad OTH exome

AF:

0.843

GnomAD4 exome

AF:

0.806

AC:

1160698

AN:

1439214

Hom.:

469249

Cov.:

AF XY:

0.808

AC XY:

579451

AN XY:

717342

show subpopulations

Gnomad4 AFR exome

AF:

0.803

Gnomad4 AMR exome

AF:

0.879

Gnomad4 ASJ exome

AF:

0.912

Gnomad4 EAS exome

AF:

0.726

Gnomad4 SAS exome

AF:

0.827

Gnomad4 FIN exome

AF:

0.722

Gnomad4 NFE exome

AF:

0.805

Gnomad4 OTH exome

AF:

0.823

GnomAD4 genome

AF:

0.809

AC:

122954

AN:

152028

Hom.:

49925

Cov.:

AF XY:

0.805

AC XY:

59809

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.810

Gnomad4 AMR

AF:

0.866

Gnomad4 ASJ

AF:

0.908

Gnomad4 EAS

AF:

0.741

Gnomad4 SAS

AF:

0.807

Gnomad4 FIN

AF:

0.709

Gnomad4 NFE

AF:

0.809

Gnomad4 OTH

AF:

0.850

Alfa

AF:

0.824

Hom.:

121330

Bravo

AF:

0.823

Asia WGS

AF:

0.795

AC:

2766

AN:

3478

EpiCase

AF:

0.831

EpiControl

AF:

0.831

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 08, 2014	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 21, 2017	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 15312511) -

Primary open angle glaucoma

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Amyotrophic lateral sclerosis type 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.8

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000023

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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