rs3740341

Variant names:

• chr10-86666285-G-A
• rs3740341
• NM_033282.4:c.*534G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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 -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 rank	MANE	Protein	UniProt
OPN4	NM_033282.4	c.*534G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000241891.10	NP_150598.1
LOC105378409	XR_001747526.2	n.265C>T		non_coding_transcript_exon_variant	Exon 1 of 3
OPN4	NM_001030015.3	c.*534G>A		3_prime_UTR_variant	Exon 11 of 11		NP_001025186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPN4	ENST00000241891.10	c.*534G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_033282.4	ENSP00000241891.5
ENSG00000289258	ENST00000443292.2	c.1432-509G>A		intron_variant	Intron 10 of 17	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

African (AFR) AF: 0.163 AC: 174 AN: 1068

American (AMR) AF: 0.268 AC: 813 AN: 3038

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 107 AN: 776

East Asian (EAS) AF: 0.460 AC: 698 AN: 1518

South Asian (SAS) AF: 0.157 AC: 510 AN: 3240

European-Finnish (FIN) AF: 0.159 AC: 195 AN: 1226

Middle Eastern (MID) AF: 0.171 AC: 25 AN: 146

European-Non Finnish (NFE) AF: 0.133 AC: 2744 AN: 20600

Other (OTH) AF: 0.164 AC: 296 AN: 1806

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

African (AFR) AF: 0.173 AC: 7205 AN: 41536

American (AMR) AF: 0.243 AC: 3715 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3470

East Asian (EAS) AF: 0.442 AC: 2284 AN: 5162

South Asian (SAS) AF: 0.194 AC: 939 AN: 4830

European-Finnish (FIN) AF: 0.160 AC: 1694 AN: 10606

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9229 AN: 68022

Other (OTH) AF: 0.176 AC: 372 AN: 2112

Alfa AF: 0.153 Hom.: 2764

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
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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: rs3740341; hg19: chr10-88426042;