NM_001008212.2:c.1243-371A>G

Variant names:

• chr10-13127374-A-G
• rs825411
• NM_001008212.2:c.1243-371A>G

Variant summary

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

The NM_001008212.2(OPTN):​c.1243-371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,128 control chromosomes in the GnomAD database, including 20,362 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 0.52 (20362 hom., cov: 33)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 13 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 (SAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.1243-371A>G		intron_variant	Intron 11 of 14	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.1243-371A>G		intron_variant	Intron 12 of 15		NP_001008212.1
OPTN	NM_001008213.1	c.1243-371A>G		intron_variant	Intron 12 of 15		NP_001008214.1
OPTN	NM_021980.4	c.1243-371A>G		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.1243-371A>G		intron_variant	Intron 11 of 14	1	NM_001008212.2	ENSP00000368021.3

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78620 AN: 152010 Hom.: 20340 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.517 AC: 78687 AN: 152128 Hom.: 20362 Cov.: 33 AF XY: 0.514 AC XY: 38195 AN XY: 74370

African (AFR) AF: 0.486 AC: 20146 AN: 41466

American (AMR) AF: 0.486 AC: 7437 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2072 AN: 3472

East Asian (EAS) AF: 0.441 AC: 2281 AN: 5178

South Asian (SAS) AF: 0.574 AC: 2770 AN: 4822

European-Finnish (FIN) AF: 0.506 AC: 5358 AN: 10586

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36870 AN: 67990

Other (OTH) AF: 0.529 AC: 1117 AN: 2112

Alfa AF: 0.536 Hom.: 91220

Bravo AF: 0.510

Asia WGS AF: 0.545 AC: 1896 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	4.6
DANN	Benign	0.35
PhyloP100		0.24
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: rs825411; hg19: chr10-13169374;