10-13108910-G-GCGCACA

Variant names:

• chr10-13108910-G-GCGCACA
• rs111744244
• NM_001008212.2:c.-11-201_-11-200insGCACAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001008212.2(OPTN):​c.-11-201_-11-200insGCACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00099 in 589,864 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 11)
  • Exomes 𝑓: 0.00060 (0 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00211 (320/151388) while in subpopulation AFR AF= 0.00692 (286/41338). AF 95% confidence interval is 0.00626. There are 2 homozygotes in gnomad4. There are 155 alleles in male gnomad4 subpopulation. Median coverage is 11. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.-11-201_-11-200insGCACAC		intron_variant	Intron 2 of 14	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.-80-51_-80-50insGCACAC		intron_variant	Intron 2 of 15		NP_001008212.1
OPTN	NM_001008213.1	c.-65-51_-65-50insGCACAC		intron_variant	Intron 2 of 15		NP_001008214.1
OPTN	NM_021980.4	c.-11-201_-11-200insGCACAC		intron_variant	Intron 1 of 13		NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.-11-202_-11-201insCGCACA		intron_variant	Intron 2 of 14	1	NM_001008212.2	ENSP00000368021.3

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 317 AN: 151274 Hom.: 2 Cov.: 11

Gnomad AFR AF: 0.00687

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000330

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000573

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000251

Gnomad OTH AF: 0.00193

GnomAD4 exome AF: 0.000602 AC: 264 AN: 438476 Hom.: 0 AF XY: 0.000627 AC XY: 147 AN XY: 234288

Gnomad4 AFR exome AF: 0.00752

Gnomad4 AMR exome AF: 0.00160

Gnomad4 ASJ exome AF: 0.000282

Gnomad4 EAS exome AF: 0.000218

Gnomad4 SAS exome AF: 0.000978

Gnomad4 FIN exome AF: 0.000619

Gnomad4 NFE exome AF: 0.000126

Gnomad4 OTH exome AF: 0.000450

GnomAD4 genome AF: 0.00211 AC: 320 AN: 151388 Hom.: 2 Cov.: 11 AF XY: 0.00210 AC XY: 155 AN XY: 73960

Gnomad4 AFR AF: 0.00692

Gnomad4 AMR AF: 0.000329

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000573

Gnomad4 NFE AF: 0.000251

Gnomad4 OTH AF: 0.00191

ClinVar

Not reported in ClinVar

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;