10-86657207-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The ENST00000372071.7(OPN4):c.303T>G(p.Arg101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 780,756 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (6 hom.)
• Consequence: OPN4 ENST00000372071.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.939

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-86657207-T-G is Benign according to our data. Variant chr10-86657207-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2640652.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.939 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN4	NM_033282.4	c.291-825T>G		intron_variant		ENST00000241891.10
OPN4	NM_001030015.3	c.303T>G	p.Arg101=	synonymous_variant	3/11
OPN4	XM_017016955.2	c.303T>G	p.Arg101=	synonymous_variant	3/10
OPN4	XM_017016956.2	c.291-825T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN4	ENST00000372071.7	c.303T>G	p.Arg101=	synonymous_variant	3/11	1
OPN4	ENST00000241891.10	c.291-825T>G		intron_variant		1	NM_033282.4	P1
OPN4	ENST00000690949.1	n.304T>G		non_coding_transcript_exon_variant	3/11

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 345 AN: 152198 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00365

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00232 AC: 576 AN: 248702 Hom.: 1 AF XY: 0.00229 AC XY: 309 AN XY: 134650

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000851

Gnomad FIN exome AF: 0.00471

Gnomad NFE exome AF: 0.00346

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00276 AC: 1734 AN: 628440 Hom.: 6 Cov.: 0 AF XY: 0.00265 AC XY: 907 AN XY: 342336

Gnomad4 AFR exome AF: 0.000339

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.000238

Gnomad4 EAS exome AF: 0.0000277

Gnomad4 SAS exome AF: 0.000703

Gnomad4 FIN exome AF: 0.00377

Gnomad4 NFE exome AF: 0.00381

Gnomad4 OTH exome AF: 0.00245

GnomAD4 genome AF: 0.00227 AC: 345 AN: 152316 Hom.: 2 Cov.: 32 AF XY: 0.00230 AC XY: 171 AN XY: 74484

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.00365

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00282 Hom.: 0

Bravo AF: 0.00207

EpiCase AF: 0.00338

EpiControl AF: 0.00320

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

OPN4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.33
Dann	Benign	0.55

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: rs41297165; hg19: chr10-88416964;