chr10-13122332-T-C

Position:

• chr10-13122332-T-C

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.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

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=-0.88).
• BP6: Variant 10-13122332-T-C is Benign according to our data. Variant chr10-13122332-T-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.780-53T>C		intron_variant		ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.780-53T>C		intron_variant			NP_001008212.1
OPTN	NM_001008213.1	c.780-53T>C		intron_variant			NP_001008214.1
OPTN	NM_021980.4	c.780-53T>C		intron_variant			NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.780-53T>C		intron_variant		1	NM_001008212.2	ENSP00000368021.3

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

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.0955

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.282

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

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.0971

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.288

Alfa AF: 0.263 Hom.: 921

Bravo AF: 0.245

Asia WGS AF: 0.199 AC: 695 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.55
DANN	Benign	0.79

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: rs765884; hg19: chr10-13164332;