10-13110666-T-G

Position:

• chr10-13110666-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000378747.8(OPTN):​c.369+190T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,042 control chromosomes in the GnomAD database, including 13,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (13513 hom., cov: 32)
• Consequence: OPTN ENST00000378747.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.50

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=-0.8).
• BP6: Variant 10-13110666-T-G is Benign according to our data. Variant chr10-13110666-T-G is described in ClinVar as [Benign]. Clinvar id is 1268826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.369+190T>G		intron_variant		ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.369+190T>G		intron_variant			NP_001008212.1
OPTN	NM_001008213.1	c.369+190T>G		intron_variant			NP_001008214.1
OPTN	NM_021980.4	c.369+190T>G		intron_variant			NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.369+190T>G		intron_variant		1	NM_001008212.2	ENSP00000368021	P3

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59261 AN: 151924 Hom.: 13513 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.390 AC: 59268 AN: 152042 Hom.: 13513 Cov.: 32 AF XY: 0.386 AC XY: 28711 AN XY: 74302

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.375

Alfa AF: 0.480 Hom.: 22013

Bravo AF: 0.365

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.65

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: rs7921853; hg19: chr10-13152666;