Genetic Variant OPA1:c.611-19T>C (chr3-193618850-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_130837.3(OPA1):c.611-19T>C 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 1,593,068 control chromosomes in the GnomAD database, including 149,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14298 hom., cov: 32)

Exomes 𝑓: 0.43 ( 134840 hom. )

Consequence

OPA1
NM_130837.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.02

Publications

24 publications found

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-AS1 (HGNC:40421): (OPA1 antisense RNA 1)

OPA1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-193618850-T-C is Benign according to our data. Variant chr3-193618850-T-C is described in ClinVar as Benign. ClinVar VariationId is 95728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130837.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OPA1	NM_130837.3	MANE Select	c.611-19T>C	intron	N/A	NP_570850.2	O60313-10
OPA1	NM_130836.3		c.557-19T>C	intron	N/A	NP_570849.2	O60313-2
OPA1	NM_130835.3		c.503-19T>C	intron	N/A	NP_570848.1	E5KLJ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OPA1	ENST00000361510.8	TSL:5 MANE Select	c.611-19T>C	intron	N/A	ENSP00000355324.2	O60313-10
OPA1	ENST00000361908.8	TSL:1	c.557-19T>C	intron	N/A	ENSP00000354681.3	O60313-2
OPA1	ENST00000968586.1		c.611-19T>C	intron	N/A	ENSP00000638645.1

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65259

AN:

151804

Hom.:

14285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.411

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.435

Gnomad OTH

AF:

0.415

GnomAD2 exomes

AF:

0.425

AC:

106737

AN:

251250

AF XY:

0.421

show subpopulations

Gnomad AFR exome

AF:

0.422

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.332

Gnomad FIN exome

AF:

0.547

Gnomad NFE exome

AF:

0.437

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.429

AC:

618431

AN:

1441146

Hom.:

134840

Cov.:

AF XY:

0.427

AC XY:

306556

AN XY:

718102

show subpopulations

African (AFR)

AF:

0.425

AC:

14059

AN:

33066

American (AMR)

AF:

0.401

AC:

17917

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

11107

AN:

25976

East Asian (EAS)

AF:

0.286

AC:

11300

AN:

39578

South Asian (SAS)

AF:

0.379

AC:

32546

AN:

85936

European-Finnish (FIN)

AF:

0.544

AC:

28975

AN:

53296

Middle Eastern (MID)

AF:

0.373

AC:

2142

AN:

5742

European-Non Finnish (NFE)

AF:

0.435

AC:

475235

AN:

1093210

Other (OTH)

AF:

0.422

AC:

25150

AN:

59640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

14995

29989

44984

59978

74973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14290

28580

42870

57160

71450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.430

AC:

65315

AN:

151922

Hom.:

14298

Cov.:

AF XY:

0.432

AC XY:

32057

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.418

AC:

17306

AN:

41428

American (AMR)

AF:

0.411

AC:

6282

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1454

AN:

3468

East Asian (EAS)

AF:

0.332

AC:

1710

AN:

5152

South Asian (SAS)

AF:

0.375

AC:

1804

AN:

4814

European-Finnish (FIN)

AF:

0.543

AC:

5713

AN:

10522

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.435

AC:

29589

AN:

67950

Other (OTH)

AF:

0.417

AC:

878

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1884

3769

5653

7538

9422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.393

Hom.:

3277

Bravo

AF:

0.423

Asia WGS

AF:

0.351

AC:

1221

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.17

(source)

DANN

Benign

0.53

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over