rs9831900

Positions:

• chr3-193648185-T-A
• chr3-193648185-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_130837.3(OPA1):​c.1935+51T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000959 in 1,397,482 control chromosomes in the GnomAD database, including 3 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 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000096 (3 hom.)
• Consequence: OPA1 NM_130837.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High Homozygotes in GnomAdExome4 at 3 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPA1	NM_130837.3	c.1935+51T>A		intron_variant		ENST00000361510.8	NP_570850.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPA1	ENST00000361510.8	c.1935+51T>A		intron_variant		5	NM_130837.3	ENSP00000355324.2

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 151980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000181 AC: 44 AN: 242784 Hom.: 0 AF XY: 0.000236 AC XY: 31 AN XY: 131168

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000206

Gnomad ASJ exome AF: 0.000505

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000303

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000175

Gnomad OTH exome AF: 0.000672

GnomAD4 exome AF: 0.0000964 AC: 120 AN: 1245384 Hom.: 3 Cov.: 17 AF XY: 0.000122 AC XY: 77 AN XY: 630090

Gnomad4 AFR exome AF: 0.0000343

Gnomad4 AMR exome AF: 0.000227

Gnomad4 ASJ exome AF: 0.000404

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000320

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000578

Gnomad4 OTH exome AF: 0.000188

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74336

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000200 Hom.: 1955

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.19
DANN	Benign	0.19
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: rs9831900; hg19: chr3-193365974;