10-13108909-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001008212.2(OPTN):​c.-11-203T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 592,040 control chromosomes in the GnomAD database, including 38,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 9589 hom., cov: 30)
Exomes 𝑓: 0.36 ( 28940 hom. )

Consequence

OPTN
NM_001008212.2 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00
Variant links:
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=-0.92).
BP6
Variant 10-13108909-T-C is Benign according to our data. Variant chr10-13108909-T-C is described in ClinVar as [Benign]. Clinvar id is 1295362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OPTNNM_001008212.2 linkuse as main transcriptc.-11-203T>C intron_variant ENST00000378747.8 NP_001008213.1 Q96CV9-1
OPTNNM_001008211.1 linkuse as main transcriptc.-80-53T>C intron_variant NP_001008212.1 Q96CV9-1
OPTNNM_001008213.1 linkuse as main transcriptc.-65-53T>C intron_variant NP_001008214.1 Q96CV9-1
OPTNNM_021980.4 linkuse as main transcriptc.-11-203T>C intron_variant NP_068815.2 Q96CV9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OPTNENST00000378747.8 linkuse as main transcriptc.-11-203T>C intron_variant 1 NM_001008212.2 ENSP00000368021.3 Q96CV9-1

Frequencies

GnomAD3 genomes
AF:
0.357
AC:
53946
AN:
151286
Hom.:
9581
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.343
Gnomad AMI
AF:
0.155
Gnomad AMR
AF:
0.391
Gnomad ASJ
AF:
0.427
Gnomad EAS
AF:
0.497
Gnomad SAS
AF:
0.398
Gnomad FIN
AF:
0.251
Gnomad MID
AF:
0.436
Gnomad NFE
AF:
0.358
Gnomad OTH
AF:
0.392
GnomAD4 exome
AF:
0.361
AC:
158923
AN:
440640
Hom.:
28940
AF XY:
0.361
AC XY:
85095
AN XY:
235396
show subpopulations
Gnomad4 AFR exome
AF:
0.336
Gnomad4 AMR exome
AF:
0.389
Gnomad4 ASJ exome
AF:
0.428
Gnomad4 EAS exome
AF:
0.442
Gnomad4 SAS exome
AF:
0.372
Gnomad4 FIN exome
AF:
0.254
Gnomad4 NFE exome
AF:
0.354
Gnomad4 OTH exome
AF:
0.367
GnomAD4 genome
AF:
0.356
AC:
53969
AN:
151400
Hom.:
9589
Cov.:
30
AF XY:
0.356
AC XY:
26303
AN XY:
73980
show subpopulations
Gnomad4 AFR
AF:
0.342
Gnomad4 AMR
AF:
0.391
Gnomad4 ASJ
AF:
0.427
Gnomad4 EAS
AF:
0.497
Gnomad4 SAS
AF:
0.397
Gnomad4 FIN
AF:
0.251
Gnomad4 NFE
AF:
0.358
Gnomad4 OTH
AF:
0.396
Alfa
AF:
0.352
Hom.:
1154
Bravo
AF:
0.368
Asia WGS
AF:
0.490
AC:
1703
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 18, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
2.4
DANN
Benign
0.10
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12415802; hg19: chr10-13150909; COSMIC: COSV53809983; COSMIC: COSV53809983; API