10-13109036-A-G

Position:

• chr10-13109036-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001008212.2(OPTN):​c.-11-76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,344,390 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (12 hom., cov: 31)
  • Exomes 𝑓: 0.00073 (10 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-13109036-A-G is Benign according to our data. Variant chr10-13109036-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1201573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00722 (1100/152292) while in subpopulation AFR AF= 0.025 (1041/41558). AF 95% confidence interval is 0.0238. There are 12 homozygotes in gnomad4. There are 522 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.-11-76A>G		intron_variant		ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.-27+21A>G		intron_variant			NP_001008212.1
OPTN	NM_001008213.1	c.-12+21A>G		intron_variant			NP_001008214.1
OPTN	NM_021980.4	c.-11-76A>G		intron_variant			NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.-11-76A>G		intron_variant		1	NM_001008212.2	ENSP00000368021.3

Frequencies

GnomAD3 genomes AF: 0.00722 AC: 1098 AN: 152174 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.000731 AC: 871 AN: 1192098 Hom.: 10 Cov.: 17 AF XY: 0.000598 AC XY: 363 AN XY: 606578

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.000991

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000780

Gnomad4 SAS exome AF: 0.0000743

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000115

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00722 AC: 1100 AN: 152292 Hom.: 12 Cov.: 31 AF XY: 0.00701 AC XY: 522 AN XY: 74468

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00655 Hom.: 1

Bravo AF: 0.00826

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1761802; hg19: chr10-13151036;