rs2675694

chr10-86664494-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.1398+692G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 152,246 control chromosomes in the GnomAD database, including 172 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 0.030 (172 hom., cov: 33)
• Consequence: OPN4 NM_033282.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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]

LOC105378409 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN4	NM_033282.4	c.1398+692G>A		intron_variant		ENST00000241891.10
LOC105378409	XR_001747526.2	n.320-1515C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN4	ENST00000241891.10	c.1398+692G>A		intron_variant		1	NM_033282.4	P1
OPN4	ENST00000372071.7	c.1431+692G>A		intron_variant		1
OPN4	ENST00000690949.1	n.1432+692G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4527 AN: 152128 Hom.: 165 Cov.: 33

Gnomad AFR AF: 0.00700

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0437

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0565

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0299 AC: 4546 AN: 152246 Hom.: 172 Cov.: 33 AF XY: 0.0312 AC XY: 2325 AN XY: 74446

Gnomad4 AFR AF: 0.00703

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0438

Gnomad4 FIN AF: 0.0350

Gnomad4 NFE AF: 0.0257

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.0395 Hom.: 82

Bravo AF: 0.0376

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	22
Dann	Benign	0.74

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: rs2675694; hg19: chr10-88424251;