NM_001008211.1:c.-382T>C

Variant names:

Variant summary

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

The NM_001008211.1(OPTN):c.-382T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 153,162 control chromosomes in the GnomAD database, including 10,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10237 hom., cov: 33)

Exomes 𝑓: 0.30 ( 64 hom. )

Consequence

OPTN
NM_001008211.1 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.49

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:

CCDC3 (HGNC:23813): (coiled-coil domain containing 3) Involved in negative regulation of gene expression; negative regulation of lipid metabolic process; and negative regulation of tumor necrosis factor-mediated signaling pathway. Located in endoplasmic reticulum and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

CCDC3 links:

ENSG00000289266 (HGNC:):

ENSG00000289266 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=-0.88).

BP6

Variant 10-13100153-T-C is Benign according to our data. Variant chr10-13100153-T-C is described in ClinVar as [Benign]. Clinvar id is 299202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2 link	c.-313T>C		upstream_gene_variant		ENST00000378747.8	NP_001008213.1	Q96CV9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8 link	c.-313T>C		upstream_gene_variant		1	NM_001008212.2	ENSP00000368021.3		Q96CV9-1

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55575

AN:

151918

Hom.:

10229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.372

GnomAD4 exome

AF:

0.302

AC:

343

AN:

1134

Hom.:

Cov.:

AF XY:

0.308

AC XY:

208

AN XY:

676

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.333

Gnomad4 EAS exome

AF:

0.333

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.317

Gnomad4 OTH exome

AF:

0.375

GnomAD4 genome

AF:

0.366

AC:

55615

AN:

152028

Hom.:

10237

Cov.:

AF XY:

0.363

AC XY:

26984

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.399

Gnomad4 AMR

AF:

0.400

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.350

Gnomad4 OTH

AF:

0.371

Alfa

AF:

0.362

Hom.:

2637

Bravo

AF:

0.375

Asia WGS

AF:

0.287

AC:

988

AN:

3454

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis type 12

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Primary open angle glaucoma

Benign:1

Jan 13, 2018

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

-0.88

CADD

Benign

0.80

DANN

Benign

0.26

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