rs1561570

Variant names:

• chr10-13113726-T-C
• rs1561570
• NM_001008212.2:c.552+1091T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 53 publications found

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]

OPTN Gene-Disease associations (from GenCC):

• glaucoma, normal tension, susceptibility to

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• amyotrophic lateral sclerosis type 12

  Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
• glaucoma 1, open angle, E

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.552+1091T>C		intron_variant	Intron 5 of 14	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.552+1091T>C		intron_variant	Intron 6 of 15		NP_001008212.1
OPTN	NM_001008213.1	c.552+1091T>C		intron_variant	Intron 6 of 15		NP_001008214.1
OPTN	NM_021980.4	c.552+1091T>C		intron_variant	Intron 4 of 13		NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.552+1091T>C		intron_variant	Intron 5 of 14	1	NM_001008212.2	ENSP00000368021.3

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

African (AFR) AF: 0.303 AC: 12546 AN: 41418

American (AMR) AF: 0.502 AC: 7661 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1791 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2770 AN: 5162

South Asian (SAS) AF: 0.464 AC: 2234 AN: 4810

European-Finnish (FIN) AF: 0.492 AC: 5201 AN: 10570

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32369 AN: 67954

Other (OTH) AF: 0.452 AC: 954 AN: 2112

Alfa AF: 0.470 Hom.: 74453

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
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1561570; hg19: chr10-13155726;