rs9831772

chr3-193648150-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.892

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]

LOC102724808 (HGNC:):

ACMG classification

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	UniProt
OPA1	NM_130837.3	c.1935+16T>G		intron_variant		ENST00000361510.8
LOC102724808	XR_924835.3	n.421-840A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPA1	ENST00000361510.8	c.1935+16T>G		intron_variant		5	NM_130837.3	A1

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11809 AN: 152136 Hom.: 512 Cov.: 32

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

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.: 24 AF XY: 0.0793 AC XY: 56113 AN XY: 707986

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.: 32 AF XY: 0.0794 AC XY: 5909 AN XY: 74448

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 05, 2016	- -
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:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	15
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

Other links and lift over

dbSNP: rs9831772; hg19: chr3-193365939; COSMIC: COSV62479527; COSMIC: COSV62479527;