3-193618850-T-C

Variant names:

• chr3-193618850-T-C
• rs3772393
• NM_130837.3:c.611-19T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130837.3(OPA1):​c.611-19T>C 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 1,593,068 control chromosomes in the GnomAD database, including 149,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14298 hom., cov: 32)
  • Exomes 𝑓: 0.43 (134840 hom.)
• Consequence: OPA1 NM_130837.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.02
• Publications: 24 publications found

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-AS1 (HGNC:40421): (OPA1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-193618850-T-C is Benign according to our data. Variant chr3-193618850-T-C is described in ClinVar as Benign. ClinVar VariationId is 95728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130837.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPA1	NM_130837.3	MANE Select	c.611-19T>C		intron	N/A	NP_570850.2
	OPA1	NM_130836.3		c.557-19T>C		intron	N/A	NP_570849.2
	OPA1	NM_130835.3		c.503-19T>C		intron	N/A	NP_570848.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPA1	ENST00000361510.8	TSL:5 MANE Select	c.611-19T>C		intron	N/A	ENSP00000355324.2
	OPA1	ENST00000361908.8	TSL:1	c.557-19T>C		intron	N/A	ENSP00000354681.3
	OPA1	ENST00000968586.1		c.611-19T>C		intron	N/A	ENSP00000638645.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65259 AN: 151804 Hom.: 14285 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.415

GnomAD2 exomes AF: 0.425 AC: 106737 AN: 251250 AF XY: 0.421

Gnomad AFR exome AF: 0.422

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.332

Gnomad FIN exome AF: 0.547

Gnomad NFE exome AF: 0.437

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.429 AC: 618431 AN: 1441146 Hom.: 134840 Cov.: 28 AF XY: 0.427 AC XY: 306556 AN XY: 718102

African (AFR) AF: 0.425 AC: 14059 AN: 33066

American (AMR) AF: 0.401 AC: 17917 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 11107 AN: 25976

East Asian (EAS) AF: 0.286 AC: 11300 AN: 39578

South Asian (SAS) AF: 0.379 AC: 32546 AN: 85936

European-Finnish (FIN) AF: 0.544 AC: 28975 AN: 53296

Middle Eastern (MID) AF: 0.373 AC: 2142 AN: 5742

European-Non Finnish (NFE) AF: 0.435 AC: 475235 AN: 1093210

Other (OTH) AF: 0.422 AC: 25150 AN: 59640

GnomAD4 genome AF: 0.430 AC: 65315 AN: 151922 Hom.: 14298 Cov.: 32 AF XY: 0.432 AC XY: 32057 AN XY: 74258

African (AFR) AF: 0.418 AC: 17306 AN: 41428

American (AMR) AF: 0.411 AC: 6282 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1454 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1710 AN: 5152

South Asian (SAS) AF: 0.375 AC: 1804 AN: 4814

European-Finnish (FIN) AF: 0.543 AC: 5713 AN: 10522

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29589 AN: 67950

Other (OTH) AF: 0.417 AC: 878 AN: 2106

Alfa AF: 0.393 Hom.: 3277

Bravo AF: 0.423

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.53
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3772393; hg19: chr3-193336639; COSMIC: COSV62479005;