rs11202106

chr10-86654813-G-Achr10-86654813-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_033282.4(OPN4):c.30G>A(p.Pro10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,352,062 control chromosomes in the GnomAD database, including 62,460 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. Synonymous variant affecting the same amino acid position (i.e. P10P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.25 (5415 hom., cov: 32)
  • Exomes 𝑓: 0.36 (57045 hom.)
• Consequence: OPN4 NM_033282.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.12

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP7: Synonymous conserved (PhyloP=-6.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN4	NM_033282.4	c.30G>A	p.Pro10=	synonymous_variant	1/10	ENST00000241891.10
OPN4	NM_001030015.3	c.30G>A	p.Pro10=	synonymous_variant	1/11
OPN4	XM_017016955.2	c.30G>A	p.Pro10=	synonymous_variant	1/10
OPN4	XM_017016956.2	c.30G>A	p.Pro10=	synonymous_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN4	ENST00000241891.10	c.30G>A	p.Pro10=	synonymous_variant	1/10	1	NM_033282.4	P1
OPN4	ENST00000372071.7	c.30G>A	p.Pro10=	synonymous_variant	1/11	1
OPN4	ENST00000690949.1	n.145+151G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.254 AC: 37538 AN: 147736 Hom.: 5408 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.288 AC: 72297 AN: 250662 Hom.: 11489 AF XY: 0.301 AC XY: 40844 AN XY: 135588

Gnomad AFR exome AF: 0.0943

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.344

Gnomad EAS exome AF: 0.256

Gnomad SAS exome AF: 0.408

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.278

GnomAD4 exome AF: 0.359 AC: 431962 AN: 1204204 Hom.: 57045 Cov.: 35 AF XY: 0.361 AC XY: 218496 AN XY: 604612

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.415

Gnomad4 FIN exome AF: 0.366

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.348

GnomAD4 genome AF: 0.254 AC: 37558 AN: 147858 Hom.: 5415 Cov.: 32 AF XY: 0.256 AC XY: 18454 AN XY: 72096

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.220

Alfa AF: 0.292 Hom.: 2927

Bravo AF: 0.223

Asia WGS AF: 0.328 AC: 1140 AN: 3478

EpiCase AF: 0.304

EpiControl AF: 0.301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.61
Dann	Benign	0.36

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: rs11202106; hg19: chr10-88414570; COSMIC: COSV54116757;