10-13127374-A-G

Position:

• chr10-13127374-A-G

Variant summary

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

The NM_001008212.2(OPTN):​c.1243-371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,128 control chromosomes in the GnomAD database, including 20,362 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 0.52 (20362 hom., cov: 33)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.1243-371A>G		intron_variant		ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.1243-371A>G		intron_variant			NP_001008212.1
OPTN	NM_001008213.1	c.1243-371A>G		intron_variant			NP_001008214.1
OPTN	NM_021980.4	c.1243-371A>G		intron_variant			NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.1243-371A>G		intron_variant		1	NM_001008212.2	ENSP00000368021	P3

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78620 AN: 152010 Hom.: 20340 Cov.: 33

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.517 AC: 78687 AN: 152128 Hom.: 20362 Cov.: 33 AF XY: 0.514 AC XY: 38195 AN XY: 74370

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.529

Alfa AF: 0.540 Hom.: 43000

Bravo AF: 0.510

Asia WGS AF: 0.545 AC: 1896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.6
DANN	Benign	0.35

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: rs825411; hg19: chr10-13169374;