rs11258211
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001008212.2(OPTN):c.626+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,587,480 control chromosomes in the GnomAD database, including 803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.032 ( 170 hom., cov: 32)
Exomes 𝑓: 0.014 ( 633 hom. )
Consequence
OPTN
NM_001008212.2 intron
NM_001008212.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.17
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 10-13116364-G-A is Benign according to our data. Variant chr10-13116364-G-A is described in ClinVar as [Benign]. Clinvar id is 256883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.08 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPTN | NM_001008212.2 | c.626+24G>A | intron_variant | ENST00000378747.8 | |||
OPTN | NM_001008211.1 | c.626+24G>A | intron_variant | ||||
OPTN | NM_001008213.1 | c.626+24G>A | intron_variant | ||||
OPTN | NM_021980.4 | c.626+24G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPTN | ENST00000378747.8 | c.626+24G>A | intron_variant | 1 | NM_001008212.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0322 AC: 4900AN: 152156Hom.: 166 Cov.: 32
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GnomAD3 exomes AF: 0.0251 AC: 6274AN: 250110Hom.: 180 AF XY: 0.0234 AC XY: 3171AN XY: 135382
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GnomAD4 exome AF: 0.0136 AC: 19507AN: 1435206Hom.: 633 Cov.: 25 AF XY: 0.0142 AC XY: 10181AN XY: 715624
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GnomAD4 genome ? AF: 0.0324 AC: 4932AN: 152274Hom.: 170 Cov.: 32 AF XY: 0.0328 AC XY: 2442AN XY: 74452
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 21, 2018 | This variant is associated with the following publications: (PMID: 12939304) - |
Primary open angle glaucoma;C1842026:Glaucoma 1, open angle, E;C3150692:Amyotrophic lateral sclerosis type 12 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at