rs10906308

Variant names:

• chr10-13128467-G-A
• rs10906308
• NM_001008212.2:c.1401+564G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-13128467-G-A
• chr10-13128467-G-T

Variant summary

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

The NM_001008212.2(OPTN):​c.1401+564G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 116,622 control chromosomes in the GnomAD database, including 2,686 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 0.21 (2686 hom., cov: 23)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 10 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: SD, AR, AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Laboratory for Molecular Medicine
• 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 (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008212.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPTN	NM_001008212.2	MANE Select	c.1401+564G>A		intron	N/A	NP_001008213.1	Q96CV9-1
	OPTN	NM_001008211.1		c.1401+564G>A		intron	N/A	NP_001008212.1	Q96CV9-1
	OPTN	NM_001008213.1		c.1401+564G>A		intron	N/A	NP_001008214.1	Q96CV9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPTN	ENST00000378747.8	TSL:1 MANE Select	c.1401+564G>A		intron	N/A	ENSP00000368021.3	Q96CV9-1
	OPTN	ENST00000378748.7	TSL:1	c.1401+564G>A		intron	N/A	ENSP00000368022.3	Q96CV9-1
	OPTN	ENST00000378757.6	TSL:1	c.1401+564G>A		intron	N/A	ENSP00000368032.2	Q96CV9-1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 24916 AN: 116592 Hom.: 2682 Cov.: 23

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.214 AC: 24931 AN: 116622 Hom.: 2686 Cov.: 23 AF XY: 0.218 AC XY: 12074 AN XY: 55410

African (AFR) AF: 0.143 AC: 4054 AN: 28276

American (AMR) AF: 0.169 AC: 1874 AN: 11094

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 660 AN: 3000

East Asian (EAS) AF: 0.323 AC: 1305 AN: 4038

South Asian (SAS) AF: 0.306 AC: 1135 AN: 3706

European-Finnish (FIN) AF: 0.333 AC: 2036 AN: 6116

Middle Eastern (MID) AF: 0.240 AC: 46 AN: 192

European-Non Finnish (NFE) AF: 0.231 AC: 13369 AN: 57850

Other (OTH) AF: 0.191 AC: 300 AN: 1572

Alfa AF: 0.209 Hom.: 5942

Bravo AF: 0.181

Asia WGS AF: 0.245 AC: 838 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.75
DANN	Benign	0.20
PhyloP100		-0.36
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: rs10906308; hg19: chr10-13170467;