10-86654813-G-C

Position:

• chr10-86654813-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6 BP7 BS1

The NM_033282.4(OPN4):​c.30G>C​(p.Pro10=) 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. Variant has been reported in Lovd as Likely benign (no stars).

• 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

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 -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 10-86654813-G-C is Benign according to our data. Variant chr10-86654813-G-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-6.12 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0123 (14096/1141702) while in subpopulation AFR AF= 0.0248 (486/19574). AF 95% confidence interval is 0.023. There are 0 homozygotes in gnomad4_exome. There are 6468 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN4	NM_033282.4	c.30G>C	p.Pro10=	synonymous_variant	1/10	ENST00000241891.10	NP_150598.1
OPN4	NM_001030015.3	c.30G>C	p.Pro10=	synonymous_variant	1/11		NP_001025186.1
OPN4	XM_017016955.2	c.30G>C	p.Pro10=	synonymous_variant	1/10		XP_016872444.1
OPN4	XM_017016956.2	c.30G>C	p.Pro10=	synonymous_variant	1/9		XP_016872445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN4	ENST00000241891.10	c.30G>C	p.Pro10=	synonymous_variant	1/10	1	NM_033282.4	ENSP00000241891	P1
OPN4	ENST00000372071.7	c.30G>C	p.Pro10=	synonymous_variant	1/11	1		ENSP00000361141
OPN4	ENST00000690949.1	n.145+151G>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.0248

Gnomad4 AMR exome AF: 0.000835

Gnomad4 ASJ exome AF: 0.00566

Gnomad4 EAS exome AF: 0.00443

Gnomad4 SAS exome AF: 0.00408

Gnomad4 FIN exome AF: 0.000890

Gnomad4 NFE exome AF: 0.0146

Gnomad4 OTH exome AF: 0.0112

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

Gnomad4 AFR AF: 0.0000496

Gnomad4 AMR AF: 0.0000671

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000214

Gnomad4 SAS AF: 0.000222

Gnomad4 FIN AF: 0.000705

Gnomad4 NFE AF: 0.0000299

Gnomad4 OTH AF: 0.00

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

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: rs11202106; hg19: chr10-88414570;