dbSNP rs10937595: OPA1:c.2872+25T>A (chr3-193666414-T-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_130837.3(OPA1):c.2872+25T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,514,964 control chromosomes in the GnomAD database, including 141,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13962 hom., cov: 32)

Exomes 𝑓: 0.43 ( 127914 hom. )

Consequence

OPA1
NM_130837.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.247

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=-0.79).

BP6

Variant 3-193666414-T-A is Benign according to our data. Variant chr3-193666414-T-A is described in ClinVar as [Benign]. Clinvar id is 1291406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-193666414-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPA1	NM_130837.3 link	c.2872+25T>A		intron_variant	Intron 28 of 30	ENST00000361510.8	NP_570850.2	O60313-10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPA1	ENST00000361510.8 link	c.2872+25T>A		intron_variant	Intron 28 of 30	5	NM_130837.3	ENSP00000355324.2		O60313-10

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64400

AN:

151968

Hom.:

13953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.385

Gnomad NFE

AF:

0.434

Gnomad OTH

AF:

0.412

GnomAD3 exomes

AF:

0.422

AC:

105860

AN:

250798

Hom.:

22889

AF XY:

0.419

AC XY:

56776

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.404

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.320

Gnomad SAS exome

AF:

0.377

Gnomad FIN exome

AF:

0.543

Gnomad NFE exome

AF:

0.436

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.430

AC:

585894

AN:

1362878

Hom.:

127914

Cov.:

AF XY:

0.428

AC XY:

292298

AN XY:

683642

show subpopulations

Gnomad4 AFR exome

AF:

0.410

Gnomad4 AMR exome

AF:

0.400

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.260

Gnomad4 SAS exome

AF:

0.378

Gnomad4 FIN exome

AF:

0.541

Gnomad4 NFE exome

AF:

0.437

Gnomad4 OTH exome

AF:

0.422

GnomAD4 genome

AF:

0.424

AC:

64454

AN:

152086

Hom.:

13962

Cov.:

AF XY:

0.426

AC XY:

31673

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.400

Gnomad4 AMR

AF:

0.409

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.539

Gnomad4 NFE

AF:

0.434

Gnomad4 OTH

AF:

0.414

Alfa

AF:

0.435

Hom.:

2661

Bravo

AF:

0.416

Asia WGS

AF:

0.344

AC:

1198

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.0

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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