10-86662359-C-T

Variant names:

• chr10-86662359-C-T
• rs1079610
• NM_033282.4:c.1181C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033282.4(OPN4):​c.1181C>T​(p.Thr394Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 1,587,300 control chromosomes in the GnomAD database, including 348,612 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37389 hom., cov: 34)
  • Exomes 𝑓: 0.66 (311223 hom.)
• Consequence: OPN4 NM_033282.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 44 publications found

Genes affected

OPN4 (HGNC:14449): (opsin 4) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This gene encodes a photoreceptive opsin protein that is expressed within the ganglion and amacrine cell layers of the retina. In mouse, retinal ganglion cell axons expressing this gene projected to the suprachiasmatic nucleus and other brain nuclei involved in circadian photoentrainment. In mouse, this protein is coupled to a transient receptor potential (TRP) ion channel through a G protein signaling pathway and produces a physiologic light response via membrane depolarization and increased intracellular calcium. The protein functions as a sensory photopigment and may also have photoisomerase activity. Experiments with knockout mice indicate that this gene attenuates, but does not abolish, photoentrainment. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ENSG00000289258 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.919383E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033282.4. 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
	OPN4	NM_033282.4	MANE Select	c.1181C>T	p.Thr394Ile	missense	Exon 8 of 10	NP_150598.1	Q9UHM6-1
	OPN4	NM_001030015.3		c.1214C>T	p.Thr405Ile	missense	Exon 9 of 11	NP_001025186.1	Q9UHM6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN4	ENST00000241891.10	TSL:1 MANE Select	c.1181C>T	p.Thr394Ile	missense	Exon 8 of 10	ENSP00000241891.5	Q9UHM6-1
	ENSG00000289258	ENST00000443292.2	TSL:1	c.1214C>T	p.Thr405Ile	missense	Exon 9 of 18	ENSP00000393132.2	C9JWU6
	OPN4	ENST00000372071.7	TSL:1	c.1214C>T	p.Thr405Ile	missense	Exon 9 of 11	ENSP00000361141.2	Q9UHM6-2

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106054 AN: 151996 Hom.: 37329 Cov.: 34

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.677

GnomAD2 exomes AF: 0.696 AC: 144303 AN: 207440 AF XY: 0.692

Gnomad AFR exome AF: 0.781

Gnomad AMR exome AF: 0.746

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.799

Gnomad FIN exome AF: 0.675

Gnomad NFE exome AF: 0.643

Gnomad OTH exome AF: 0.667

GnomAD4 exome AF: 0.657 AC: 942279 AN: 1435186 Hom.: 311223 Cov.: 56 AF XY: 0.657 AC XY: 467777 AN XY: 711478

African (AFR) AF: 0.777 AC: 25634 AN: 32994

American (AMR) AF: 0.744 AC: 30282 AN: 40684

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 17742 AN: 25542

East Asian (EAS) AF: 0.798 AC: 30707 AN: 38466

South Asian (SAS) AF: 0.737 AC: 60606 AN: 82228

European-Finnish (FIN) AF: 0.677 AC: 34060 AN: 50282

Middle Eastern (MID) AF: 0.667 AC: 3784 AN: 5672

European-Non Finnish (NFE) AF: 0.636 AC: 699814 AN: 1099900

Other (OTH) AF: 0.667 AC: 39650 AN: 59418

GnomAD4 genome AF: 0.698 AC: 106171 AN: 152114 Hom.: 37389 Cov.: 34 AF XY: 0.704 AC XY: 52336 AN XY: 74334

African (AFR) AF: 0.771 AC: 32011 AN: 41502

American (AMR) AF: 0.712 AC: 10887 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2434 AN: 3468

East Asian (EAS) AF: 0.793 AC: 4089 AN: 5154

South Asian (SAS) AF: 0.746 AC: 3596 AN: 4820

European-Finnish (FIN) AF: 0.683 AC: 7231 AN: 10582

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43579 AN: 67980

Other (OTH) AF: 0.679 AC: 1432 AN: 2110

Alfa AF: 0.657 Hom.: 74246

Bravo AF: 0.702

TwinsUK AF: 0.622 AC: 2307

ALSPAC AF: 0.638 AC: 2459

ESP6500AA AF: 0.768 AC: 3374

ESP6500EA AF: 0.646 AC: 5544

ExAC AF: 0.669 AC: 79490

Asia WGS AF: 0.773 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.80
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.79
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.053	T
MetaRNN	Benign	7.9e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PhyloP100		2.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.081
Sift	Benign	0.66	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.032
MPC		0.055
ClinPred		0.0012	T
GERP RS		1.1
Varity_R		0.042
gMVP		0.51
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1079610; hg19: chr10-88422116; COSMIC: COSV54117289;