Variant 10-13100251-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001008212.2(OPTN):c.-215G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,900 control chromosomes in the GnomAD database, including 3,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3521 hom., cov: 34)

Exomes 𝑓: 0.21 ( 23 hom. )

Consequence

OPTN
NM_001008212.2 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.169

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=-0.72).

BP6

Variant 10-13100251-G-A is Benign according to our data. Variant chr10-13100251-G-A is described in ClinVar as [Benign]. Clinvar id is 299207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
OPTN	NM_001008212.2 linkuse as main transcript	c.-215G>A	5_prime_UTR_variant	1/15	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1 linkuse as main transcript	c.-284G>A	5_prime_UTR_variant	1/16		NP_001008212.1
OPTN	NM_001008213.1 linkuse as main transcript	c.-269G>A	5_prime_UTR_variant	1/16		NP_001008214.1
OPTN	NM_021980.4 linkuse as main transcript	c.-63G>A	5_prime_UTR_variant	1/14		NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8 linkuse as main transcript	c.-215G>A		5_prime_UTR_variant	1/15	1	NM_001008212.2	ENSP00000368021	P3	Q96CV9-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29731

AN:

152076

Hom.:

3518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0523

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.224

GnomAD4 exome

AF:

0.205

AC:

147

AN:

716

Hom.:

Cov.:

AF XY:

0.221

AC XY:

101

AN XY:

456

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.195

AC:

29729

AN:

152184

Hom.:

3521

Cov.:

AF XY:

0.195

AC XY:

14482

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0521

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.176

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.226

Alfa

AF:

0.218

Hom.:

1229

Bravo

AF:

0.194

Asia WGS

AF:

0.191

AC:

660

AN:

3460

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Primary open angle glaucoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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