rs9838374

Positions:

• chr3-193598916-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.32+5507C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,074 control chromosomes in the GnomAD database, including 3,870 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 0.22 (3870 hom., cov: 32)
• Consequence: OPA1 NM_130837.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPA1	NM_130837.3	c.32+5507C>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.32+5507C>T		intron_variant		5	NM_130837.3	ENSP00000355324.2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33567 AN: 151956 Hom.: 3861 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33611 AN: 152074 Hom.: 3870 Cov.: 32 AF XY: 0.227 AC XY: 16861 AN XY: 74306

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.212

Alfa AF: 0.187 Hom.: 4742

Bravo AF: 0.222

Asia WGS AF: 0.264 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.0
DANN	Benign	0.85

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: rs9838374; hg19: chr3-193316705;