rs149752576

Positions:

chr3-193643409-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_130837.3(OPA1):c.1342A>C(p.Arg448Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00415 in 1,612,042 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 83 hom. )

Consequence

OPA1
NM_130837.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.10

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 3-193643409-A-C is Benign according to our data. Variant chr3-193643409-A-C is described in ClinVar as [Benign]. Clinvar id is 95709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-193643409-A-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00308 (469/152350) while in subpopulation SAS AF= 0.0172 (83/4826). AF 95% confidence interval is 0.0142. There are 3 homozygotes in gnomad4. There are 256 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPA1	NM_130837.3 linkuse as main transcript	c.1342A>C	p.Arg448Arg	synonymous_variant	14/31	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.1342A>C	p.Arg448Arg	synonymous_variant	14/31	5	NM_130837.3	ENSP00000355324.2		O60313-10

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

471

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00642

AC:

1612

AN:

251112

Hom.:

AF XY:

0.00782

AC XY:

1062

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.000618

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00576

Gnomad EAS exome

AF:

0.0176

Gnomad SAS exome

AF:

0.0239

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00307

Gnomad OTH exome

AF:

0.00539

GnomAD4 exome

AF:

0.00427

AC:

6226

AN:

1459692

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

3695

AN XY:

726336

show subpopulations

Gnomad4 AFR exome

AF:

0.000838

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.00663

Gnomad4 EAS exome

AF:

0.0237

Gnomad4 SAS exome

AF:

0.0239

Gnomad4 FIN exome

AF:

0.00169

Gnomad4 NFE exome

AF:

0.00219

Gnomad4 OTH exome

AF:

0.00497

GnomAD4 genome

AF:

0.00308

AC:

469

AN:

152350

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

256

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.0162

Gnomad4 SAS

AF:

0.0172

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00254

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00275

Hom.:

Bravo

AF:

0.00320

Asia WGS

AF:

0.0120

AC:

AN:

3474

EpiCase

AF:

0.00463

EpiControl

AF:

0.00486

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 23, 2014	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. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 03, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 01, 2013	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Autosomal dominant optic atrophy classic form

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

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)

0.060

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