10-13108903-TGC-TGCGCGC

Variant names:

• chr10-13108903-T-TGCGC
• rs145112217
• NM_001008212.2:c.-11-207_-11-204dupCGCG

Variant summary

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

The NM_001008212.2(OPTN):​c.-11-207_-11-204dupCGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 477,382 control chromosomes in the GnomAD database, including 829 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (364 hom., cov: 30)
  • Exomes 𝑓: 0.048 (465 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18
• 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 10-13108903-T-TGCGC is Benign according to our data. Variant chr10-13108903-T-TGCGC is described in ClinVar as Benign. ClinVar VariationId is 1260673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 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.-11-207_-11-204dupCGCG		intron	N/A	NP_001008213.1	Q96CV9-1
	OPTN	NM_001008211.1		c.-80-57_-80-54dupCGCG		intron	N/A	NP_001008212.1	Q96CV9-1
	OPTN	NM_001008213.1		c.-65-57_-65-54dupCGCG		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.-11-207_-11-204dupCGCG		intron	N/A	ENSP00000368021.3	Q96CV9-1
	OPTN	ENST00000378748.7	TSL:1	c.-80-57_-80-54dupCGCG		intron	N/A	ENSP00000368022.3	Q96CV9-1
	OPTN	ENST00000378757.6	TSL:1	c.-11-207_-11-204dupCGCG		intron	N/A	ENSP00000368032.2	Q96CV9-1

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 8922 AN: 133632 Hom.: 362 Cov.: 30

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0422

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0822

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0606

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0679

GnomAD4 exome AF: 0.0478 AC: 16417 AN: 343664 Hom.: 465 AF XY: 0.0481 AC XY: 8832 AN XY: 183552

African (AFR) AF: 0.134 AC: 1464 AN: 10892

American (AMR) AF: 0.0274 AC: 539 AN: 19676

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 951 AN: 10672

East Asian (EAS) AF: 0.111 AC: 2386 AN: 21516

South Asian (SAS) AF: 0.0591 AC: 2454 AN: 41528

European-Finnish (FIN) AF: 0.0276 AC: 565 AN: 20436

Middle Eastern (MID) AF: 0.0524 AC: 69 AN: 1316

European-Non Finnish (NFE) AF: 0.0344 AC: 6825 AN: 198416

Other (OTH) AF: 0.0606 AC: 1164 AN: 19212

GnomAD4 genome AF: 0.0667 AC: 8920 AN: 133718 Hom.: 364 Cov.: 30 AF XY: 0.0671 AC XY: 4375 AN XY: 65248

African (AFR) AF: 0.132 AC: 4924 AN: 37376

American (AMR) AF: 0.0359 AC: 452 AN: 12596

Ashkenazi Jewish (ASJ) AF: 0.0822 AC: 247 AN: 3006

East Asian (EAS) AF: 0.159 AC: 683 AN: 4296

South Asian (SAS) AF: 0.0619 AC: 250 AN: 4038

European-Finnish (FIN) AF: 0.0308 AC: 299 AN: 9694

Middle Eastern (MID) AF: 0.0569 AC: 14 AN: 246

European-Non Finnish (NFE) AF: 0.0317 AC: 1894 AN: 59788

Other (OTH) AF: 0.0669 AC: 119 AN: 1778

Alfa AF: 0.00629 Hom.: 0

Asia WGS AF: 0.0980 AC: 342 AN: 3472

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		-1.2
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: rs145112217; hg19: chr10-13150903; COSMIC: COSV53810520; COSMIC: COSV53810520;