10-86654812-C-T

Variant names:

• chr10-86654812-C-T
• rs2675703
• NM_033282.4:c.29C>T

Variant summary

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

The NM_001030015.3(OPN4):​c.29C>T​(p.Pro10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,610,452 control chromosomes in the GnomAD database, including 13,482 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.10 (995 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12487 hom.)
• Consequence: OPN4 NM_001030015.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• Publications: 39 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=0.001470089).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030015.3. 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
	OPN4	NM_033282.4	MANE Select	c.29C>T	p.Pro10Leu	missense	Exon 1 of 10	NP_150598.1
	OPN4	NM_001030015.3		c.29C>T	p.Pro10Leu	missense	Exon 1 of 11	NP_001025186.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN4	ENST00000241891.10	TSL:1 MANE Select	c.29C>T	p.Pro10Leu	missense	Exon 1 of 10	ENSP00000241891.5
	ENSG00000289258	ENST00000443292.2	TSL:1	c.29C>T	p.Pro10Leu	missense	Exon 1 of 18	ENSP00000393132.2
	OPN4	ENST00000372071.7	TSL:1	c.29C>T	p.Pro10Leu	missense	Exon 1 of 11	ENSP00000361141.2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15605 AN: 152120 Hom.: 996 Cov.: 33

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.105 AC: 26254 AN: 250784 AF XY: 0.108

Gnomad AFR exome AF: 0.0391

Gnomad AMR exome AF: 0.0738

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.0391

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.126 AC: 183175 AN: 1458214 Hom.: 12487 Cov.: 32 AF XY: 0.125 AC XY: 90470 AN XY: 725218

African (AFR) AF: 0.0383 AC: 1282 AN: 33440

American (AMR) AF: 0.0792 AC: 3536 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3706 AN: 26092

East Asian (EAS) AF: 0.0512 AC: 2028 AN: 39640

South Asian (SAS) AF: 0.0743 AC: 6400 AN: 86164

European-Finnish (FIN) AF: 0.114 AC: 6085 AN: 53234

Middle Eastern (MID) AF: 0.146 AC: 839 AN: 5736

European-Non Finnish (NFE) AF: 0.137 AC: 151917 AN: 1109020

Other (OTH) AF: 0.123 AC: 7382 AN: 60228

GnomAD4 genome AF: 0.103 AC: 15612 AN: 152238 Hom.: 995 Cov.: 33 AF XY: 0.102 AC XY: 7629 AN XY: 74432

African (AFR) AF: 0.0398 AC: 1653 AN: 41564

American (AMR) AF: 0.116 AC: 1770 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3468

East Asian (EAS) AF: 0.0445 AC: 230 AN: 5170

South Asian (SAS) AF: 0.0771 AC: 372 AN: 4826

European-Finnish (FIN) AF: 0.115 AC: 1216 AN: 10608

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9321 AN: 67990

Other (OTH) AF: 0.110 AC: 232 AN: 2110

Alfa AF: 0.124 Hom.: 4063

Bravo AF: 0.100

TwinsUK AF: 0.144 AC: 535

ALSPAC AF: 0.133 AC: 511

ESP6500AA AF: 0.0399 AC: 176

ESP6500EA AF: 0.135 AC: 1161

ExAC AF: 0.105 AC: 12797

Asia WGS AF: 0.0630 AC: 217 AN: 3478

EpiCase AF: 0.141

EpiControl AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.42
DANN	Benign	0.27
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.77
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.085
Sift	Benign	0.72	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.064
MPC		0.052
ClinPred		0.00052	T
GERP RS		-2.1
PromoterAI		0.015	Neutral
Varity_R		0.017
gMVP		0.22
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2675703; hg19: chr10-88414569; COSMIC: COSV54115835;