10-86657967-C-T

Variant names:

• chr10-86657967-C-T
• rs10788521
• NM_033282.4:c.291-65C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033282.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN4	NM_033282.4	MANE Select	c.291-65C>T		intron	N/A	NP_150598.1	Q9UHM6-1
	OPN4	NM_001030015.3		c.324-65C>T		intron	N/A	NP_001025186.1	Q9UHM6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN4	ENST00000241891.10	TSL:1 MANE Select	c.291-65C>T		intron	N/A	ENSP00000241891.5	Q9UHM6-1
	ENSG00000289258	ENST00000443292.2	TSL:1	c.324-65C>T		intron	N/A	ENSP00000393132.2	C9JWU6
	OPN4	ENST00000372071.7	TSL:1	c.324-65C>T		intron	N/A	ENSP00000361141.2	Q9UHM6-2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37653 AN: 151862 Hom.: 5458 Cov.: 32

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

African (AFR) AF: 0.0909 AC: 2851 AN: 31356

American (AMR) AF: 0.154 AC: 5810 AN: 37636

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 7864 AN: 22944

East Asian (EAS) AF: 0.261 AC: 10288 AN: 39398

South Asian (SAS) AF: 0.404 AC: 31246 AN: 77284

European-Finnish (FIN) AF: 0.334 AC: 16517 AN: 49490

Middle Eastern (MID) AF: 0.263 AC: 1017 AN: 3870

European-Non Finnish (NFE) AF: 0.318 AC: 344017 AN: 1080316

Other (OTH) AF: 0.296 AC: 17170 AN: 57932

GnomAD4 genome AF: 0.248 AC: 37670 AN: 151980 Hom.: 5464 Cov.: 32 AF XY: 0.249 AC XY: 18517 AN XY: 74260

African (AFR) AF: 0.0969 AC: 4023 AN: 41496

American (AMR) AF: 0.176 AC: 2688 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3466

East Asian (EAS) AF: 0.269 AC: 1380 AN: 5138

South Asian (SAS) AF: 0.394 AC: 1890 AN: 4794

European-Finnish (FIN) AF: 0.337 AC: 3557 AN: 10558

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22072 AN: 67926

Other (OTH) AF: 0.218 AC: 461 AN: 2116

Alfa AF: 0.280 Hom.: 1719

Bravo AF: 0.223

Asia WGS AF: 0.329 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.082
DANN	Benign	0.74
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10788521; hg19: chr10-88417724; COSMIC: COSV54116774;