rs9851685

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_130837.3(OPA1):c.2274T>C(p.Ala758Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,612,978 control chromosomes in the GnomAD database, including 180,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19036 hom., cov: 32)

Exomes 𝑓: 0.47 ( 161494 hom. )

Consequence

OPA1
NM_130837.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.324

Variant links:

Genes affected

OPA1 (HGNC:8140): (OPA1 mitochondrial dynamin like GTPase) The protein encoded by this gene is a nuclear-encoded mitochondrial protein with similarity to dynamin-related GTPases. The encoded protein localizes to the inner mitochondrial membrane and helps regulate mitochondrial stability and energy output. This protein also sequesters cytochrome c. Mutations in this gene have been associated with optic atrophy type 1, which is a dominantly inherited optic neuropathy resulting in progressive loss of visual acuity, leading in many cases to legal blindness. [provided by RefSeq, Aug 2017]

OPA1 links:

OPA1 (HGNC:):

OPA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 3-193657175-T-C is Benign according to our data. Variant chr3-193657175-T-C is described in ClinVar as [Benign]. Clinvar id is 95717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-193657175-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.324 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPA1	NM_130837.3 linkuse as main transcript	c.2274T>C	p.Ala758Ala	synonymous_variant	23/31	ENST00000361510.8	NP_570850.2	O60313-10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPA1	ENST00000361510.8 linkuse as main transcript	c.2274T>C	p.Ala758Ala	synonymous_variant	23/31	5	NM_130837.3	ENSP00000355324.2		O60313-10

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75117

AN:

151774

Hom.:

19008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.564

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.470

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.472

GnomAD3 exomes

AF:

0.467

AC:

117241

AN:

251170

Hom.:

27988

AF XY:

0.463

AC XY:

62829

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.569

Gnomad AMR exome

AF:

0.421

Gnomad ASJ exome

AF:

0.476

Gnomad EAS exome

AF:

0.384

Gnomad SAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.575

Gnomad NFE exome

AF:

0.467

Gnomad OTH exome

AF:

0.456

GnomAD4 exome

AF:

0.468

AC:

684175

AN:

1461084

Hom.:

161494

Cov.:

AF XY:

0.467

AC XY:

339085

AN XY:

726830

show subpopulations

Gnomad4 AFR exome

AF:

0.576

Gnomad4 AMR exome

AF:

0.422

Gnomad4 ASJ exome

AF:

0.482

Gnomad4 EAS exome

AF:

0.333

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.570

Gnomad4 NFE exome

AF:

0.469

Gnomad4 OTH exome

AF:

0.469

GnomAD4 genome

AF:

0.495

AC:

75199

AN:

151894

Hom.:

19036

Cov.:

AF XY:

0.495

AC XY:

36754

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.564

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.470

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.425

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.468

Gnomad4 OTH

AF:

0.473

Alfa

AF:

0.480

Hom.:

10575

Bravo

AF:

0.490

Asia WGS

AF:

0.420

AC:

1461

AN:

3478

EpiCase

AF:

0.453

EpiControl

AF:

0.450

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 23, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2011	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 19, 2016	- -

Autosomal dominant optic atrophy classic form

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 28, 2017	- -

Abortive cerebellar ataxia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type)

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.5

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over