10-13110666-T-G

Variant names:

• chr10-13110666-T-G
• rs7921853
• NM_001008212.2:c.369+190T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001008212.2(OPTN):​c.369+190T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,042 control chromosomes in the GnomAD database, including 13,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (13513 hom., cov: 32)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.50
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-13110666-T-G is Benign according to our data. Variant chr10-13110666-T-G is described in ClinVar as Benign. ClinVar VariationId is 1268826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.369+190T>G		intron_variant	Intron 4 of 14	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.369+190T>G		intron_variant	Intron 5 of 15		NP_001008212.1
OPTN	NM_001008213.1	c.369+190T>G		intron_variant	Intron 5 of 15		NP_001008214.1
OPTN	NM_021980.4	c.369+190T>G		intron_variant	Intron 3 of 13		NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.369+190T>G		intron_variant	Intron 4 of 14	1	NM_001008212.2	ENSP00000368021.3

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59261 AN: 151924 Hom.: 13513 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.390 AC: 59268 AN: 152042 Hom.: 13513 Cov.: 32 AF XY: 0.386 AC XY: 28711 AN XY: 74302

African (AFR) AF: 0.165 AC: 6866 AN: 41492

American (AMR) AF: 0.335 AC: 5122 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1022 AN: 5170

South Asian (SAS) AF: 0.438 AC: 2107 AN: 4816

European-Finnish (FIN) AF: 0.515 AC: 5427 AN: 10546

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35538 AN: 67950

Other (OTH) AF: 0.375 AC: 791 AN: 2112

Alfa AF: 0.467 Hom.: 27289

Bravo AF: 0.365

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

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	-0.80
CADD	Benign	12
DANN	Benign	0.65
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7921853; hg19: chr10-13152666;