rs765884

Variant names:

• chr10-13122332-T-C
• rs765884
• NM_001008212.2:c.780-53T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-13122332-T-C
• chr10-13122332-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001008212.2(OPTN):​c.780-53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,269,060 control chromosomes in the GnomAD database, including 49,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4860 hom., cov: 33)
  • Exomes 𝑓: 0.28 (44617 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0530
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-13122332-T-C is Benign according to our data. Variant chr10-13122332-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008212.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPTN	NM_001008212.2	MANE Select	c.780-53T>C		intron	N/A	NP_001008213.1
	OPTN	NM_001008211.1		c.780-53T>C		intron	N/A	NP_001008212.1
	OPTN	NM_001008213.1		c.780-53T>C		intron	N/A	NP_001008214.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPTN	ENST00000378747.8	TSL:1 MANE Select	c.780-53T>C		intron	N/A	ENSP00000368021.3
	OPTN	ENST00000378748.7	TSL:1	c.780-53T>C		intron	N/A	ENSP00000368022.3
	OPTN	ENST00000378757.6	TSL:1	c.780-53T>C		intron	N/A	ENSP00000368032.2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36851 AN: 152108 Hom.: 4868 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.0967

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.278 AC: 310993 AN: 1116832 Hom.: 44617 AF XY: 0.278 AC XY: 158932 AN XY: 571302

African (AFR) AF: 0.162 AC: 4285 AN: 26398

American (AMR) AF: 0.263 AC: 10940 AN: 41606

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 8781 AN: 23956

East Asian (EAS) AF: 0.0955 AC: 3589 AN: 37570

South Asian (SAS) AF: 0.235 AC: 18296 AN: 77906

European-Finnish (FIN) AF: 0.196 AC: 10302 AN: 52688

Middle Eastern (MID) AF: 0.399 AC: 1855 AN: 4646

European-Non Finnish (NFE) AF: 0.298 AC: 239183 AN: 803208

Other (OTH) AF: 0.282 AC: 13762 AN: 48854

GnomAD4 genome AF: 0.242 AC: 36855 AN: 152228 Hom.: 4860 Cov.: 33 AF XY: 0.237 AC XY: 17646 AN XY: 74434

African (AFR) AF: 0.161 AC: 6699 AN: 41550

American (AMR) AF: 0.267 AC: 4084 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1262 AN: 3472

East Asian (EAS) AF: 0.0971 AC: 503 AN: 5180

South Asian (SAS) AF: 0.224 AC: 1082 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2053 AN: 10602

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20172 AN: 67994

Other (OTH) AF: 0.288 AC: 607 AN: 2110

Alfa AF: 0.263 Hom.: 921

Bravo AF: 0.245

Asia WGS AF: 0.199 AC: 695 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.55
DANN	Benign	0.79
PhyloP100		-0.053
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: rs765884; hg19: chr10-13164332;