Variant rs10788521 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033282.4(OPN4):c.291-65C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,552,206 control chromosomes in the GnomAD database, including 75,595 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 ( 5464 hom., cov: 32)

Exomes 𝑓: 0.31 ( 70131 hom. )

Consequence

OPN4
NM_033282.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.64

Variant links:

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]

OPN4 links:

ENSG00000289258 (HGNC:):

ENSG00000289258 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
OPN4	NM_033282.4 link	c.291-65C>T	intron_variant	ENST00000241891.10	NP_150598.1	Q9UHM6-1
OPN4	NM_001030015.3 link	c.324-65C>T	intron_variant		NP_001025186.1	Q9UHM6-2
OPN4	XM_017016955.2 link	c.324-65C>T	intron_variant		XP_016872444.1
OPN4	XM_017016956.2 link	c.291-65C>T	intron_variant		XP_016872445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN4	ENST00000241891.10 link	c.291-65C>T		intron_variant		1	NM_033282.4	ENSP00000241891.5		Q9UHM6-1
ENSG00000289258	ENST00000443292.2 link	c.324-65C>T		intron_variant		1		ENSP00000393132.2		C9JWU6

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37653

AN:

151862

Hom.:

5458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0972

Gnomad AMI

AF:

0.352

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.312

AC:

436780

AN:

1400226

Hom.:

70131

AF XY:

0.316

AC XY:

219367

AN XY:

694820

show subpopulations

Gnomad4 AFR exome

AF:

0.0909

Gnomad4 AMR exome

AF:

0.154

Gnomad4 ASJ exome

AF:

0.343

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.404

Gnomad4 FIN exome

AF:

0.334

Gnomad4 NFE exome

AF:

0.318

Gnomad4 OTH exome

AF:

0.296

GnomAD4 genome

AF:

0.248

AC:

37670

AN:

151980

Hom.:

5464

Cov.:

AF XY:

0.249

AC XY:

18517

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.0969

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.353

Gnomad4 EAS

AF:

0.269

Gnomad4 SAS

AF:

0.394

Gnomad4 FIN

AF:

0.337

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.218

Alfa

AF:

0.283

Hom.:

1715

Bravo

AF:

0.223

Asia WGS

AF:

0.329

AC:

1143

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.082

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over