10-13108910-G-GCACACA

Position:

• chr10-13108910-G-GCACACA

Variant summary

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

The NM_001008212.2(OPTN):​c.-11-192_-11-187dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 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

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-GCACACA is Benign according to our data. Variant chr10-13108910-G-GCACACA is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTN	NM_001008212.2	c.-11-192_-11-187dup		intron_variant		ENST00000378747.8
OPTN	NM_001008211.1	c.-80-42_-80-37dup		intron_variant
OPTN	NM_001008213.1	c.-65-42_-65-37dup		intron_variant
OPTN	NM_021980.4	c.-11-192_-11-187dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTN	ENST00000378747.8	c.-11-192_-11-187dup		intron_variant		1	NM_001008212.2	P3

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

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.00587

Gnomad4 EAS exome AF: 0.000839

Gnomad4 SAS exome AF: 0.00649

Gnomad4 FIN exome AF: 0.00558

Gnomad4 NFE exome AF: 0.00695

Gnomad4 OTH exome AF: 0.0144

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

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.00579

Gnomad4 EAS AF: 0.000779

Gnomad4 SAS AF: 0.00666

Gnomad4 FIN AF: 0.00554

Gnomad4 NFE AF: 0.00639

Gnomad4 OTH AF: 0.0340

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

Mar 10, 2020

- -

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;