10-13136697-C-A

Variant names:

• chr10-13136697-C-A
• rs10906310
• NM_001008212.2:c.1613-48C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021980.4(OPTN):​c.1613-48C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,610,842 control chromosomes in the GnomAD database, including 50,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4886 hom., cov: 32)
  • Exomes 𝑓: 0.25 (45912 hom.)
• Consequence: OPTN NM_021980.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.246
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• glaucoma, normal tension, susceptibility to

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• amyotrophic lateral sclerosis type 12

  Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
• glaucoma 1, open angle, E

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-13136697-C-A is Benign according to our data. Variant chr10-13136697-C-A is described in ClinVar as Benign. ClinVar VariationId is 256879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021980.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPTN	NM_001008212.2	MANE Select	c.1613-48C>A		intron	N/A	NP_001008213.1
	OPTN	NM_001008211.1		c.1613-48C>A		intron	N/A	NP_001008212.1
	OPTN	NM_001008213.1		c.1613-48C>A		intron	N/A	NP_001008214.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPTN	ENST00000378747.8	TSL:1 MANE Select	c.1613-48C>A		intron	N/A	ENSP00000368021.3
	OPTN	ENST00000378748.7	TSL:1	c.1613-48C>A		intron	N/A	ENSP00000368022.3
	OPTN	ENST00000378757.6	TSL:1	c.1613-48C>A		intron	N/A	ENSP00000368032.2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38428 AN: 151808 Hom.: 4882 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.220

GnomAD2 exomes AF: 0.262 AC: 65023 AN: 247764 AF XY: 0.266

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.335

Gnomad FIN exome AF: 0.314

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.246 AC: 358170 AN: 1458918 Hom.: 45912 Cov.: 31 AF XY: 0.249 AC XY: 180511 AN XY: 725736

African (AFR) AF: 0.259 AC: 8659 AN: 33400

American (AMR) AF: 0.217 AC: 9654 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 5957 AN: 26076

East Asian (EAS) AF: 0.387 AC: 15348 AN: 39646

South Asian (SAS) AF: 0.342 AC: 29428 AN: 86056

European-Finnish (FIN) AF: 0.315 AC: 16743 AN: 53196

Middle Eastern (MID) AF: 0.168 AC: 968 AN: 5754

European-Non Finnish (NFE) AF: 0.231 AC: 256821 AN: 1110020

Other (OTH) AF: 0.242 AC: 14592 AN: 60270

GnomAD4 genome AF: 0.253 AC: 38456 AN: 151924 Hom.: 4886 Cov.: 32 AF XY: 0.255 AC XY: 18967 AN XY: 74238

African (AFR) AF: 0.263 AC: 10911 AN: 41424

American (AMR) AF: 0.205 AC: 3138 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 799 AN: 3466

East Asian (EAS) AF: 0.341 AC: 1759 AN: 5152

South Asian (SAS) AF: 0.347 AC: 1666 AN: 4808

European-Finnish (FIN) AF: 0.310 AC: 3264 AN: 10520

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16133 AN: 67960

Other (OTH) AF: 0.221 AC: 466 AN: 2104

Alfa AF: 0.245 Hom.: 3195

Bravo AF: 0.242

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.40
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10906310; hg19: chr10-13178697; COSMIC: COSV53810548; COSMIC: COSV53810548;