10-13108850-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001008212.2(OPTN):c.-11-262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 434,180 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (16 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (3 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.183

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-13108850-T-C is Benign according to our data. Variant chr10-13108850-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1197618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00759 (1155/152114) while in subpopulation AFR AF= 0.0258 (1070/41506). AF 95% confidence interval is 0.0245. There are 16 homozygotes in gnomad4. There are 548 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTN	NM_001008212.2	c.-11-262T>C		intron_variant		ENST00000378747.8
OPTN	NM_001008211.1	c.-80-112T>C		intron_variant
OPTN	NM_001008213.1	c.-65-112T>C		intron_variant
OPTN	NM_021980.4	c.-11-262T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTN	ENST00000378747.8	c.-11-262T>C		intron_variant		1	NM_001008212.2	P3

Frequencies

GnomAD3 genomes AF: 0.00761 AC: 1156 AN: 151996 Hom.: 16 Cov.: 31

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00480

GnomAD4 exome AF: 0.00114 AC: 321 AN: 282066 Hom.: 3 AF XY: 0.000943 AC XY: 143 AN XY: 151584

Gnomad4 AFR exome AF: 0.0265

Gnomad4 AMR exome AF: 0.00127

Gnomad4 ASJ exome AF: 0.00405

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000470

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000104

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.00759 AC: 1155 AN: 152114 Hom.: 16 Cov.: 31 AF XY: 0.00737 AC XY: 548 AN XY: 74392

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.00155 Hom.: 0

Bravo AF: 0.00883

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

Mar 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.3
Dann	Benign	0.78

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

Other links and lift over

dbSNP: rs142468336; hg19: chr10-13150850;