rs10788521

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-86657967-C-A
• chr10-86657967-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000443292.2(ENSG00000289258):​c.324-65C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,401,984 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ENSG00000289258 ENST00000443292.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443292.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1401984 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 695632

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31370

American (AMR) AF: 0.00 AC: 0 AN: 37670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39420

South Asian (SAS) AF: 0.00 AC: 0 AN: 77366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3874

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1081782

Other (OTH) AF: 0.00 AC: 0 AN: 57976

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.023
DANN	Benign	0.79
PhyloP100		-2.6

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: rs10788521; hg19: chr10-88417724;