10-13108850-T-C

Variant names:

• chr10-13108850-T-C
• rs142468336
• NM_001008212.2:c.-11-262T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• 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

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.-11-262T>C		intron_variant	Intron 2 of 14	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.-80-112T>C		intron_variant	Intron 2 of 15		NP_001008212.1
OPTN	NM_001008213.1	c.-65-112T>C		intron_variant	Intron 2 of 15		NP_001008214.1
OPTN	NM_021980.4	c.-11-262T>C		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.-11-262T>C		intron_variant	Intron 2 of 14	1	NM_001008212.2	ENSP00000368021.3

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 AC: 222 AN: 8362

Gnomad4 AMR exome AF: 0.00127 AC: 18 AN: 14178

Gnomad4 ASJ exome AF: 0.00405 AC: 33 AN: 8150

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 16272

Gnomad4 SAS exome AF: 0.0000470 AC: 2 AN: 42546

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 13200

Gnomad4 NFE exome AF: 0.000104 AC: 17 AN: 162970

Gnomad4 Remaining exome AF: 0.00177 AC: 27 AN: 15262

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 AC: 0.0257794 AN: 0.0257794

Gnomad4 AMR AF: 0.00301 AC: 0.00301363 AN: 0.00301363

Gnomad4 ASJ AF: 0.00519 AC: 0.00519331 AN: 0.00519331

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000415 AC: 0.000414594 AN: 0.000414594

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000118 AC: 0.000117696 AN: 0.000117696

Gnomad4 OTH AF: 0.00475 AC: 0.00475285 AN: 0.00475285

Alfa AF: 0.00155 Hom.: 0

Bravo AF: 0.00883

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 17, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.78
Mutation Taster		=100/0	polymorphism

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;