chr10-13108910-G-GCACACA

Variant names:

• chr10-13108910-G-GCACACA
• rs71386156
• NM_001008212.2:c.-11-192_-11-187dupACACAC

Variant summary

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

The NM_001008212.2(OPTN):​c.-11-192_-11-187dupACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 588,650 control chromosomes in the GnomAD database, including 387 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (343 hom., cov: 11)
  • Exomes 𝑓: 0.010 (44 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):

• 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 -10 ACMG points.

• BP6: Variant 10-13108910-G-GCACACA is Benign according to our data. Variant chr10-13108910-G-GCACACA is described in ClinVar as Benign. ClinVar VariationId is 1259327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 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.-11-192_-11-187dupACACAC		intron	N/A	NP_001008213.1	Q96CV9-1
	OPTN	NM_001008211.1		c.-80-42_-80-37dupACACAC		intron	N/A	NP_001008212.1	Q96CV9-1
	OPTN	NM_001008213.1		c.-65-42_-65-37dupACACAC		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.-11-192_-11-187dupACACAC		intron	N/A	ENSP00000368021.3	Q96CV9-1
	OPTN	ENST00000378748.7	TSL:1	c.-80-42_-80-37dupACACAC		intron	N/A	ENSP00000368022.3	Q96CV9-1
	OPTN	ENST00000378757.6	TSL:1	c.-11-192_-11-187dupACACAC		intron	N/A	ENSP00000368032.2	Q96CV9-1

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6044 AN: 151240 Hom.: 339 Cov.: 11

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.00579

Gnomad EAS AF: 0.000777

Gnomad SAS AF: 0.00666

Gnomad FIN AF: 0.00554

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00639

Gnomad OTH AF: 0.0343

GnomAD4 exome AF: 0.0102 AC: 4471 AN: 437296 Hom.: 44 AF XY: 0.00954 AC XY: 2229 AN XY: 233674

African (AFR) AF: 0.112 AC: 1464 AN: 13024

American (AMR) AF: 0.0109 AC: 293 AN: 26848

Ashkenazi Jewish (ASJ) AF: 0.00587 AC: 83 AN: 14130

East Asian (EAS) AF: 0.000839 AC: 23 AN: 27420

South Asian (SAS) AF: 0.00649 AC: 324 AN: 49938

European-Finnish (FIN) AF: 0.00558 AC: 144 AN: 25822

Middle Eastern (MID) AF: 0.0135 AC: 25 AN: 1854

European-Non Finnish (NFE) AF: 0.00695 AC: 1764 AN: 253844

Other (OTH) AF: 0.0144 AC: 351 AN: 24416

GnomAD4 genome AF: 0.0401 AC: 6063 AN: 151354 Hom.: 343 Cov.: 11 AF XY: 0.0393 AC XY: 2909 AN XY: 73942

African (AFR) AF: 0.123 AC: 5092 AN: 41314

American (AMR) AF: 0.0231 AC: 351 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00579 AC: 20 AN: 3454

East Asian (EAS) AF: 0.000779 AC: 4 AN: 5136

South Asian (SAS) AF: 0.00666 AC: 32 AN: 4804

European-Finnish (FIN) AF: 0.00554 AC: 58 AN: 10468

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00639 AC: 433 AN: 67710

Other (OTH) AF: 0.0340 AC: 71 AN: 2090

Alfa AF: 0.00339 Hom.: 154

ClinVar

ClinVar submissions as Germline

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;