rs1561570

chr10-13113726-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001008212.2(OPTN):c.552+1091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,968 control chromosomes in the GnomAD database, including 14,912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (14912 hom., cov: 31)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTN	NM_001008212.2	c.552+1091T>C		intron_variant		ENST00000378747.8
OPTN	NM_001008211.1	c.552+1091T>C		intron_variant
OPTN	NM_001008213.1	c.552+1091T>C		intron_variant
OPTN	NM_021980.4	c.552+1091T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTN	ENST00000378747.8	c.552+1091T>C		intron_variant		1	NM_001008212.2	P3

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66093 AN: 151848 Hom.: 14908 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.435 AC: 66119 AN: 151968 Hom.: 14912 Cov.: 31 AF XY: 0.439 AC XY: 32626 AN XY: 74276

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.452

Alfa AF: 0.478 Hom.: 38607

Bravo AF: 0.432

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.0
Dann	Benign	0.29

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: rs1561570; hg19: chr10-13155726;