10-13108910-G-GCACA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001008212.2(OPTN):c.-11-190_-11-187dup 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTN	NM_001008212.2	c.-11-190_-11-187dup		intron_variant		ENST00000378747.8
OPTN	NM_001008211.1	c.-80-40_-80-37dup		intron_variant
OPTN	NM_001008213.1	c.-65-40_-65-37dup		intron_variant
OPTN	NM_021980.4	c.-11-190_-11-187dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTN	ENST00000378747.8	c.-11-190_-11-187dup		intron_variant		1	NM_001008212.2	P3

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

Gnomad4 AFR exome AF: 0.0691

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.265

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

Gnomad4 AFR AF: 0.0715

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.286

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71386156; hg19: chr10-13150910;