NM_001008212.2:c.1243-679G>A

Variant names:

• chr10-13127066-G-A
• rs17512962
• NM_001008212.2:c.1243-679G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001008212.2(OPTN):​c.1243-679G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,156 control chromosomes in the GnomAD database, including 4,303 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4303 hom., cov: 32)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 33 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.1243-679G>A		intron_variant	Intron 11 of 14	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.1243-679G>A		intron_variant	Intron 12 of 15		NP_001008212.1
OPTN	NM_001008213.1	c.1243-679G>A		intron_variant	Intron 12 of 15		NP_001008214.1
OPTN	NM_021980.4	c.1243-679G>A		intron_variant	Intron 10 of 13		NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.1243-679G>A		intron_variant	Intron 11 of 14	1	NM_001008212.2	ENSP00000368021.3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33743 AN: 152038 Hom.: 4309 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.222 AC: 33740 AN: 152156 Hom.: 4303 Cov.: 32 AF XY: 0.217 AC XY: 16139 AN XY: 74386

African (AFR) AF: 0.114 AC: 4719 AN: 41530

American (AMR) AF: 0.255 AC: 3894 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1196 AN: 3472

East Asian (EAS) AF: 0.0972 AC: 504 AN: 5186

South Asian (SAS) AF: 0.218 AC: 1049 AN: 4804

European-Finnish (FIN) AF: 0.180 AC: 1909 AN: 10586

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19515 AN: 67992

Other (OTH) AF: 0.262 AC: 554 AN: 2112

Alfa AF: 0.270 Hom.: 26149

Bravo AF: 0.224

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		-0.024
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: rs17512962; hg19: chr10-13169066;