10-13108909-T-C

Variant names:

• chr10-13108909-T-C
• rs12415802
• NM_001008212.2:c.-11-203T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001008212.2(OPTN):​c.-11-203T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 592,040 control chromosomes in the GnomAD database, including 38,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (9589 hom., cov: 30)
  • Exomes 𝑓: 0.36 (28940 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00
• Publications: 4 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):

• amyotrophic lateral sclerosis type 12

  Inheritance: AD, SD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, ClinGen, Genomics England PanelApp
• glaucoma, normal tension, susceptibility to

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• glaucoma 1, open angle, E

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-13108909-T-C is Benign according to our data. Variant chr10-13108909-T-C is described in ClinVar as Benign. ClinVar VariationId is 1295362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 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.-11-203T>C		intron	N/A	NP_001008213.1	Q96CV9-1
	OPTN	NM_001008211.1		c.-80-53T>C		intron	N/A	NP_001008212.1	Q96CV9-1
	OPTN	NM_001008213.1		c.-65-53T>C		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.-11-203T>C		intron	N/A	ENSP00000368021.3	Q96CV9-1
	OPTN	ENST00000378748.7	TSL:1	c.-80-53T>C		intron	N/A	ENSP00000368022.3	Q96CV9-1
	OPTN	ENST00000378757.6	TSL:1	c.-11-203T>C		intron	N/A	ENSP00000368032.2	Q96CV9-1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 53946 AN: 151286 Hom.: 9581 Cov.: 30

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.361 AC: 158923 AN: 440640 Hom.: 28940 AF XY: 0.361 AC XY: 85095 AN XY: 235396

African (AFR) AF: 0.336 AC: 4409 AN: 13134

American (AMR) AF: 0.389 AC: 10493 AN: 26998

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 6106 AN: 14278

East Asian (EAS) AF: 0.442 AC: 12184 AN: 27540

South Asian (SAS) AF: 0.372 AC: 18918 AN: 50914

European-Finnish (FIN) AF: 0.254 AC: 6509 AN: 25646

Middle Eastern (MID) AF: 0.435 AC: 821 AN: 1886

European-Non Finnish (NFE) AF: 0.354 AC: 90436 AN: 255568

Other (OTH) AF: 0.367 AC: 9047 AN: 24676

GnomAD4 genome AF: 0.356 AC: 53969 AN: 151400 Hom.: 9589 Cov.: 30 AF XY: 0.356 AC XY: 26303 AN XY: 73980

African (AFR) AF: 0.342 AC: 14142 AN: 41302

American (AMR) AF: 0.391 AC: 5944 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1477 AN: 3456

East Asian (EAS) AF: 0.497 AC: 2535 AN: 5100

South Asian (SAS) AF: 0.397 AC: 1904 AN: 4800

European-Finnish (FIN) AF: 0.251 AC: 2638 AN: 10510

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24235 AN: 67744

Other (OTH) AF: 0.396 AC: 828 AN: 2092

Alfa AF: 0.352 Hom.: 1154

Bravo AF: 0.368

Asia WGS AF: 0.490 AC: 1703 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.10
PhyloP100		0.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs12415802; hg19: chr10-13150909; COSMIC: COSV53809983; COSMIC: COSV53809983;