rs11202106

Variant names:

• chr10-86654813-G-A
• rs11202106
• NM_033282.4:c.30G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-86654813-G-A
• chr10-86654813-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_033282.4(OPN4):​c.30G>A​(p.Pro10Pro) 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.

• 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
• Publications: 18 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 -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 rank	MANE	Protein	UniProt
OPN4	NM_033282.4	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 1 of 10	ENST00000241891.10	NP_150598.1
OPN4	NM_001030015.3	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 1 of 11		NP_001025186.1
OPN4	XM_017016955.2	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 1 of 10		XP_016872444.1
OPN4	XM_017016956.2	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 1 of 9		XP_016872445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPN4	ENST00000241891.10	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 1 of 10	1	NM_033282.4	ENSP00000241891.5
ENSG00000289258	ENST00000443292.2	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 1 of 18	1		ENSP00000393132.2

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

GnomAD2 exomes AF: 0.288 AC: 72297 AN: 250662 AF XY: 0.301

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 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

African (AFR) AF: 0.140 AC: 3032 AN: 21720

American (AMR) AF: 0.168 AC: 6888 AN: 40982

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 8709 AN: 22942

East Asian (EAS) AF: 0.343 AC: 10119 AN: 29500

South Asian (SAS) AF: 0.415 AC: 34185 AN: 82314

European-Finnish (FIN) AF: 0.366 AC: 17379 AN: 47474

Middle Eastern (MID) AF: 0.286 AC: 1414 AN: 4952

European-Non Finnish (NFE) AF: 0.368 AC: 333206 AN: 905440

Other (OTH) AF: 0.348 AC: 17030 AN: 48880

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

African (AFR) AF: 0.100 AC: 4041 AN: 40344

American (AMR) AF: 0.180 AC: 2683 AN: 14902

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1223 AN: 3416

East Asian (EAS) AF: 0.295 AC: 1376 AN: 4670

South Asian (SAS) AF: 0.412 AC: 1857 AN: 4508

European-Finnish (FIN) AF: 0.351 AC: 3488 AN: 9924

Middle Eastern (MID) AF: 0.188 AC: 54 AN: 288

European-Non Finnish (NFE) AF: 0.330 AC: 22059 AN: 66808

Other (OTH) AF: 0.220 AC: 460 AN: 2094

Alfa AF: 0.289 Hom.: 2931

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
PhyloP100		-6.1
PromoterAI		-0.0020	Neutral
Mutation Taster		=10/90	disease causing

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