rs12415716

Variant names:

• chr10-13138287-T-G
• rs12415716
• NM_001008212.2:c.*1421T>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001008212.2(OPTN):​c.*1421T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 178,626 control chromosomes in the GnomAD database, including 5,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4496 hom., cov: 33)
  • Exomes 𝑓: 0.25 (895 hom.)
• Consequence: OPTN NM_001008212.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.339

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-13138287-T-G is Benign according to our data. Variant chr10-13138287-T-G is described in ClinVar as [Benign]. Clinvar id is 368895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.*1421T>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.*1421T>G		downstream_gene_variant			NP_001008212.1
OPTN	NM_001008213.1	c.*1421T>G		downstream_gene_variant			NP_001008214.1
OPTN	NM_021980.4	c.*1421T>G		downstream_gene_variant			NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.*1421T>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_001008212.2	ENSP00000368021.3
OPTN	ENST00000378748.7	c.*1421T>G		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000368022.3
OPTN	ENST00000378757.6	c.*1421T>G		3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000368032.2
OPTN	ENST00000378752.7	c.*1421T>G		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000368027.3

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34970 AN: 152074 Hom.: 4502 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.0980

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.248 AC: 6554 AN: 26434 Hom.: 895 Cov.: 0 AF XY: 0.250 AC XY: 3030 AN XY: 12110

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.0882

Gnomad4 SAS exome AF: 0.273

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.230 AC: 34969 AN: 152192 Hom.: 4496 Cov.: 33 AF XY: 0.225 AC XY: 16727 AN XY: 74386

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.0984

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.267

Alfa AF: 0.230 Hom.: 672

Bravo AF: 0.232

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Amyotrophic Lateral Sclerosis, Recessive Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary open angle glaucoma Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: 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	-0.75
CADD	Benign	5.0
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12415716; hg19: chr10-13180287;