10-13108910-G-GCACA

Variant names:

• chr10-13108910-G-GCACA
• rs71386156
• NM_001008212.2:c.-11-190_-11-187dupACAC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001008212.2(OPTN):​c.-11-190_-11-187dupACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 588,430 control chromosomes in the GnomAD database, including 16,183 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4929 hom., cov: 11)
  • Exomes 𝑓: 0.27 (11254 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.777
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 10-13108910-G-GCACA is Benign according to our data. Variant chr10-13108910-G-GCACA is described in ClinVar as Benign. ClinVar VariationId is 1259042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 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.-11-190_-11-187dupACAC		intron	N/A	NP_001008213.1	Q96CV9-1
	OPTN	NM_001008211.1		c.-80-40_-80-37dupACAC		intron	N/A	NP_001008212.1	Q96CV9-1
	OPTN	NM_001008213.1		c.-65-40_-65-37dupACAC		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.-11-190_-11-187dupACAC		intron	N/A	ENSP00000368021.3	Q96CV9-1
	OPTN	ENST00000378748.7	TSL:1	c.-80-40_-80-37dupACAC		intron	N/A	ENSP00000368022.3	Q96CV9-1
	OPTN	ENST00000378757.6	TSL:1	c.-11-190_-11-187dupACAC		intron	N/A	ENSP00000368032.2	Q96CV9-1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35692 AN: 151208 Hom.: 4928 Cov.: 11

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.272 AC: 118702 AN: 437108 Hom.: 11254 AF XY: 0.272 AC XY: 63642 AN XY: 233560

African (AFR) AF: 0.0691 AC: 896 AN: 12958

American (AMR) AF: 0.296 AC: 7949 AN: 26838

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 4561 AN: 14122

East Asian (EAS) AF: 0.261 AC: 7159 AN: 27392

South Asian (SAS) AF: 0.268 AC: 13422 AN: 50032

European-Finnish (FIN) AF: 0.198 AC: 5102 AN: 25796

Middle Eastern (MID) AF: 0.345 AC: 640 AN: 1856

European-Non Finnish (NFE) AF: 0.286 AC: 72512 AN: 253736

Other (OTH) AF: 0.265 AC: 6461 AN: 24378

GnomAD4 genome AF: 0.236 AC: 35689 AN: 151322 Hom.: 4929 Cov.: 11 AF XY: 0.235 AC XY: 17383 AN XY: 73926

African (AFR) AF: 0.0715 AC: 2953 AN: 41326

American (AMR) AF: 0.311 AC: 4719 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1196 AN: 3456

East Asian (EAS) AF: 0.279 AC: 1431 AN: 5134

South Asian (SAS) AF: 0.311 AC: 1494 AN: 4800

European-Finnish (FIN) AF: 0.204 AC: 2134 AN: 10462

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 20959 AN: 67688

Other (OTH) AF: 0.286 AC: 598 AN: 2088

Alfa AF: 0.118 Hom.: 154

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71386156; hg19: chr10-13150910; COSMIC: COSV107307642; COSMIC: COSV107307642;