10-86654813-G-C

Variant names:

• chr10-86654813-G-C
• rs11202106
• NM_033282.4:c.30G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_033282.4(OPN4):​c.30G>C​(p.Pro10Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,289,602 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: 𝑓 0.000095 (0 hom., cov: 32)
  • Exomes 𝑓: 0.012 (0 hom.)
• Consequence: OPN4 NM_033282.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.12
• Publications: 18 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 -3 ACMG points.

• PM2: Variant has high frequency in the AFR (0.023) population. However there is too low homozygotes in high coverage region: (expected more than 38, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP7: Synonymous conserved (PhyloP=-6.12 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPN4	NM_033282.4	c.30G>C	p.Pro10Pro	synonymous_variant	Exon 1 of 10	ENST00000241891.10	NP_150598.1
OPN4	NM_001030015.3	c.30G>C	p.Pro10Pro	synonymous_variant	Exon 1 of 11		NP_001025186.1
OPN4	XM_017016955.2	c.30G>C	p.Pro10Pro	synonymous_variant	Exon 1 of 10		XP_016872444.1
OPN4	XM_017016956.2	c.30G>C	p.Pro10Pro	synonymous_variant	Exon 1 of 9		XP_016872445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPN4	ENST00000241891.10	c.30G>C	p.Pro10Pro	synonymous_variant	Exon 1 of 10	1	NM_033282.4	ENSP00000241891.5
ENSG00000289258	ENST00000443292.2	c.30G>C	p.Pro10Pro	synonymous_variant	Exon 1 of 18	1		ENSP00000393132.2

Frequencies

GnomAD3 genomes AF: 0.000102 AC: 15 AN: 147776 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000745

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000672

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000214

Gnomad SAS AF: 0.000222

Gnomad FIN AF: 0.000705

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000299

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0123 AC: 14096 AN: 1141702 Hom.: 0 Cov.: 35 AF XY: 0.0112 AC XY: 6468 AN XY: 575672

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

African (AFR) AF: 0.0248 AC: 486 AN: 19574

American (AMR) AF: 0.000835 AC: 34 AN: 40720

Ashkenazi Jewish (ASJ) AF: 0.00566 AC: 127 AN: 22440

East Asian (EAS) AF: 0.00443 AC: 127 AN: 28648

South Asian (SAS) AF: 0.00408 AC: 330 AN: 80914

European-Finnish (FIN) AF: 0.000890 AC: 42 AN: 47204

Middle Eastern (MID) AF: 0.00829 AC: 40 AN: 4828

European-Non Finnish (NFE) AF: 0.0146 AC: 12389 AN: 850808

Other (OTH) AF: 0.0112 AC: 521 AN: 46566

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000947 AC: 14 AN: 147900 Hom.: 0 Cov.: 32 AF XY: 0.000139 AC XY: 10 AN XY: 72132

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

African (AFR) AF: 0.0000496 AC: 2 AN: 40350

American (AMR) AF: 0.0000671 AC: 1 AN: 14908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.000214 AC: 1 AN: 4668

South Asian (SAS) AF: 0.000222 AC: 1 AN: 4508

European-Finnish (FIN) AF: 0.000705 AC: 7 AN: 9934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000299 AC: 2 AN: 66832

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 2931

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.38
PhyloP100		-6.1
PromoterAI		0.0098	Neutral
Mutation Taster		=100/0	polymorphism

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: rs11202106; hg19: chr10-88414570;