rs10937595

Positions:

• chr3-193666414-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.247

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 -14 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_single_submitter, 1 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/exons	MANE	UniProt
OPA1	NM_130837.3	c.2872+25T>A		intron_variant		ENST00000361510.8
LOC102724808	XR_924835.3	n.420+2506A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPA1	ENST00000361510.8	c.2872+25T>A		intron_variant		5	NM_130837.3	A1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64400 AN: 151968 Hom.: 13953 Cov.: 32

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

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.: 21 AF XY: 0.428 AC XY: 292298 AN XY: 683642

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.: 32 AF XY: 0.426 AC XY: 31673 AN XY: 74366

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

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

Other links and lift over

dbSNP: rs10937595; hg19: chr3-193384203; COSMIC: COSV62479549; COSMIC: COSV62479549;