3-193668749-C-T

Position:

• chr3-193668749-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130837.3(OPA1):​c.2983+1469C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,265,718 control chromosomes in the GnomAD database, including 292,620 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (38502 hom., cov: 31)
  • Exomes 𝑓: 0.67 (254118 hom.)
• Consequence: OPA1 NM_130837.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPA1	NM_130837.3	c.2983+1469C>T		intron_variant		ENST00000361510.8	NP_570850.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPA1	ENST00000361510.8	c.2983+1469C>T		intron_variant		5	NM_130837.3	ENSP00000355324.2

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107561 AN: 151856 Hom.: 38460 Cov.: 31

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.704

GnomAD4 exome AF: 0.674 AC: 750380 AN: 1113742 Hom.: 254118 Cov.: 38 AF XY: 0.678 AC XY: 362801 AN XY: 535014

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.760

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.731

Gnomad4 SAS exome AF: 0.828

Gnomad4 FIN exome AF: 0.730

Gnomad4 NFE exome AF: 0.657

Gnomad4 OTH exome AF: 0.690

GnomAD4 genome AF: 0.708 AC: 107664 AN: 151976 Hom.: 38502 Cov.: 31 AF XY: 0.715 AC XY: 53098 AN XY: 74276

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.705

Alfa AF: 0.666 Hom.: 42789

Bravo AF: 0.710

Asia WGS AF: 0.764 AC: 2655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.010
DANN	Benign	0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs414237; hg19: chr3-193386538;