Variant rs9831772 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_130837.3(OPA1):c.1935+16T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 1,569,684 control chromosomes in the GnomAD database, including 5,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 514 hom., cov: 32)

Exomes 𝑓: 0.079 ( 4779 hom. )

Consequence

OPA1
NM_130837.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.892

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:

LOC102724808 (HGNC:):

LOC102724808 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=-0.8).

BP6

Variant 3-193648150-T-G is Benign according to our data. Variant chr3-193648150-T-G is described in ClinVar as [Benign]. Clinvar id is 95714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-193648150-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.125 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.1935+16T>G		intron_variant		ENST00000361510.8	NP_570850.2
LOC102724808	XR_924835.3 linkuse as main transcript	n.421-840A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPA1	ENST00000361510.8 linkuse as main transcript	c.1935+16T>G		intron_variant		5	NM_130837.3	ENSP00000355324	A1	O60313-10

Frequencies

GnomAD3 genomes

AF:

0.0776

AC:

11809

AN:

152136

Hom.:

512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0485

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.0785

Gnomad EAS

AF:

0.0720

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0777

Gnomad OTH

AF:

0.0921

GnomAD3 exomes

AF:

0.0891

AC:

22354

AN:

250910

Hom.:

1099

AF XY:

0.0877

AC XY:

11897

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.0466

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.0793

Gnomad EAS exome

AF:

0.0760

Gnomad SAS exome

AF:

0.0980

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0778

Gnomad OTH exome

AF:

0.0816

GnomAD4 exome

AF:

0.0789

AC:

111883

AN:

1417428

Hom.:

4779

Cov.:

AF XY:

0.0793

AC XY:

56113

AN XY:

707986

show subpopulations

Gnomad4 AFR exome

AF:

0.0449

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.0763

Gnomad4 EAS exome

AF:

0.0661

Gnomad4 SAS exome

AF:

0.0969

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.0756

Gnomad4 OTH exome

AF:

0.0771

GnomAD4 genome

AF:

0.0776

AC:

11821

AN:

152256

Hom.:

514

Cov.:

AF XY:

0.0794

AC XY:

5909

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0483

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.0785

Gnomad4 EAS

AF:

0.0720

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.0778

Gnomad4 OTH

AF:

0.0969

Alfa

AF:

0.0764

Hom.:

148

Bravo

AF:

0.0766

Asia WGS

AF:

0.0980

AC:

343

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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)	Feb 05, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 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:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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