rs3740341

Positions:

• chr10-86666285-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.*534G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 185,650 control chromosomes in the GnomAD database, including 3,167 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 (2555 hom., cov: 34)
  • Exomes 𝑓: 0.17 (612 hom.)
• Consequence: OPN4 NM_033282.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.804

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN4	NM_033282.4	c.*534G>A		3_prime_UTR_variant	10/10	ENST00000241891.10	NP_150598.1
OPN4	NM_001030015.3	c.*534G>A		3_prime_UTR_variant	11/11		NP_001025186.1
LOC105378409	XR_001747526.2	n.265C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN4	ENST00000241891.10	c.*534G>A		3_prime_UTR_variant	10/10	1	NM_033282.4	ENSP00000241891.5
ENSG00000289258	ENST00000443292.2	c.1432-509G>A		intron_variant		1		ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26066 AN: 152114 Hom.: 2554 Cov.: 34

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0870

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.166 AC: 5562 AN: 33418 Hom.: 612 Cov.: 0 AF XY: 0.167 AC XY: 2831 AN XY: 16960

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.460

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.171 AC: 26079 AN: 152232 Hom.: 2555 Cov.: 34 AF XY: 0.176 AC XY: 13109 AN XY: 74426

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.176

Alfa AF: 0.152 Hom.: 1875

Bravo AF: 0.181

Asia WGS AF: 0.278 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.69
DANN	Benign	0.76

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: rs3740341; hg19: chr10-88426042;