rs111744244

Variant names:

• chr10-13108910-G-GCGCA
• rs111744244
• NM_001008212.2:c.-11-201_-11-200insGCAC

Your query was ambiguous. Multiple possible variants found:

• chr10-13108910-G-GCGCA
• chr10-13108910-G-GCGCACA
• chr10-13108910-G-GCGCACACA
• chr10-13108910-G-GCGCACACACA
• chr10-13108910-G-GCGCGCA
• chr10-13108910-G-GCGCGCACA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001008212.2(OPTN):​c.-11-201_-11-200insGCAC 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 589,722 control chromosomes in the GnomAD database, including 193 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (44 hom., cov: 11)
  • Exomes 𝑓: 0.019 (149 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.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.-11-201_-11-200insGCAC		intron_variant	Intron 2 of 14	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.-80-51_-80-50insGCAC		intron_variant	Intron 2 of 15		NP_001008212.1
OPTN	NM_001008213.1	c.-65-51_-65-50insGCAC		intron_variant	Intron 2 of 15		NP_001008214.1
OPTN	NM_021980.4	c.-11-201_-11-200insGCAC		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_-11-201insCGCA		intron_variant	Intron 2 of 14	1	NM_001008212.2	ENSP00000368021.3

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2277 AN: 151268 Hom.: 44 Cov.: 11

Gnomad AFR AF: 0.00541

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.00405

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.0272

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.00823

GnomAD4 exome AF: 0.0189 AC: 8271 AN: 438340 Hom.: 149 AF XY: 0.0192 AC XY: 4506 AN XY: 234230

Gnomad4 AFR exome AF: 0.00683

Gnomad4 AMR exome AF: 0.0344

Gnomad4 ASJ exome AF: 0.00346

Gnomad4 EAS exome AF: 0.0712

Gnomad4 SAS exome AF: 0.0254

Gnomad4 FIN exome AF: 0.0166

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.0179

GnomAD4 genome AF: 0.0150 AC: 2277 AN: 151382 Hom.: 44 Cov.: 11 AF XY: 0.0156 AC XY: 1155 AN XY: 73956

Gnomad4 AFR AF: 0.00542

Gnomad4 AMR AF: 0.0249

Gnomad4 ASJ AF: 0.00405

Gnomad4 EAS AF: 0.0873

Gnomad4 SAS AF: 0.0273

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0115

Alfa AF: 0.00512 Hom.: 0

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;