rs3740335

Positions:

• chr10-86659884-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033282.4(OPN4):​c.801-11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,613,470 control chromosomes in the GnomAD database, including 23,987 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 0.17 (2447 hom., cov: 33)
  • Exomes 𝑓: 0.16 (21540 hom.)
• Consequence: OPN4 NM_033282.4 intron
• Scores: Splicing: ADA: 0.0002122
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN4	NM_033282.4	c.801-11G>A		intron_variant		ENST00000241891.10	NP_150598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN4	ENST00000241891.10	c.801-11G>A		intron_variant		1	NM_033282.4	ENSP00000241891.5
ENSG00000289258	ENST00000443292.2	c.834-11G>A		intron_variant		1		ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25220 AN: 152116 Hom.: 2449 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.175

GnomAD3 exomes AF: 0.199 AC: 49949 AN: 250540 Hom.: 6357 AF XY: 0.192 AC XY: 25987 AN XY: 135498

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.490

Gnomad SAS exome AF: 0.188

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.158 AC: 231168 AN: 1461236 Hom.: 21540 Cov.: 33 AF XY: 0.158 AC XY: 114730 AN XY: 726922

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.166 AC: 25225 AN: 152234 Hom.: 2447 Cov.: 33 AF XY: 0.170 AC XY: 12670 AN XY: 74418

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.174

Alfa AF: 0.145 Hom.: 385

Bravo AF: 0.174

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.40
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00021
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.040		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: rs3740335; hg19: chr10-88419641; COSMIC: COSV54118405;