chr10-13108903-T-TGCGC

Position:

• chr10-13108903-T-TGCGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001008212.2(OPTN):​c.-11-207_-11-204dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 477,382 control chromosomes in the GnomAD database, including 829 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (364 hom., cov: 30)
  • Exomes 𝑓: 0.048 (465 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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 -10 ACMG points.

• BP6: Variant 10-13108903-T-TGCGC is Benign according to our data. Variant chr10-13108903-T-TGCGC is described in ClinVar as [Benign]. Clinvar id is 1260673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTN	NM_001008212.2	c.-11-207_-11-204dup		intron_variant		ENST00000378747.8
OPTN	NM_001008211.1	c.-80-57_-80-54dup		intron_variant
OPTN	NM_001008213.1	c.-65-57_-65-54dup		intron_variant
OPTN	NM_021980.4	c.-11-207_-11-204dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTN	ENST00000378747.8	c.-11-207_-11-204dup		intron_variant		1	NM_001008212.2	P3

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 8922 AN: 133632 Hom.: 362 Cov.: 30

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0422

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0822

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0606

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0679

GnomAD4 exome AF: 0.0478 AC: 16417 AN: 343664 Hom.: 465 AF XY: 0.0481 AC XY: 8832 AN XY: 183552

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0274

Gnomad4 ASJ exome AF: 0.0891

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.0591

Gnomad4 FIN exome AF: 0.0276

Gnomad4 NFE exome AF: 0.0344

Gnomad4 OTH exome AF: 0.0606

GnomAD4 genome AF: 0.0667 AC: 8920 AN: 133718 Hom.: 364 Cov.: 30 AF XY: 0.0671 AC XY: 4375 AN XY: 65248

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0359

Gnomad4 ASJ AF: 0.0822

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.0619

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.0317

Gnomad4 OTH AF: 0.0669

Alfa AF: 0.00629 Hom.: 0

Asia WGS AF: 0.0980 AC: 342 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 14, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs145112217; hg19: chr10-13150903;