10-13108910-G-GCGCACACA

Position:

• chr10-13108910-G-GCGCACACA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001008212.2(OPTN):​c.-11-201_-11-200insGCACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 589,876 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (9 hom., cov: 11)
  • Exomes 𝑓: 0.00057 (0 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Likely 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-GCGCACACA is Benign according to our data. Variant chr10-13108910-G-GCGCACACA is described in ClinVar as [Likely_benign]. Clinvar id is 1188641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00452 (684/151390) while in subpopulation AFR AF= 0.0156 (643/41340). AF 95% confidence interval is 0.0146. There are 9 homozygotes in gnomad4. There are 313 alleles in male gnomad4 subpopulation. Median coverage is 11. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTN	NM_001008212.2	c.-11-201_-11-200insGCACACAC		intron_variant		ENST00000378747.8
OPTN	NM_001008211.1	c.-80-51_-80-50insGCACACAC		intron_variant
OPTN	NM_001008213.1	c.-65-51_-65-50insGCACACAC		intron_variant
OPTN	NM_021980.4	c.-11-201_-11-200insGCACACAC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTN	ENST00000378747.8	c.-11-201_-11-200insGCACACAC		intron_variant		1	NM_001008212.2	P3

Frequencies

GnomAD3 genomes AF: 0.00450 AC: 680 AN: 151276 Hom.: 9 Cov.: 11

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000591

Gnomad OTH AF: 0.00387

GnomAD4 exome AF: 0.000566 AC: 248 AN: 438486 Hom.: 0 AF XY: 0.000397 AC XY: 93 AN XY: 234292

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.000855

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000157

Gnomad4 OTH exome AF: 0.00110

GnomAD4 genome AF: 0.00452 AC: 684 AN: 151390 Hom.: 9 Cov.: 11 AF XY: 0.00423 AC XY: 313 AN XY: 73960

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.00191

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000591

Gnomad4 OTH AF: 0.00383

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 30, 2019

- -

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: rs111744244; hg19: chr10-13150910;