rs145009674

chrX-154153062-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020061.6(OPN1LW):c.532A>G(p.Ile178Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: OPN1LW NM_020061.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.68

Genes affected

OPN1LW (HGNC:9936): (opsin 1, long wave sensitive) This gene encodes for a light absorbing visual pigment of the opsin gene family. The encoded protein is called red cone photopigment or long-wavelength sensitive opsin. Opsins are G-protein coupled receptors with seven transmembrane domains, an N-terminal extracellular domain, and a C-terminal cytoplasmic domain. This gene and the medium-wavelength opsin gene are tandemly arrayed on the X chromosome and frequent unequal recombination and gene conversion may occur between these sequences. X chromosomes may have fusions of the medium- and long-wavelength opsin genes or may have more than one copy of these genes. Defects in this gene are the cause of partial, protanopic colorblindness. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005366087).
• BS2: High Homozygotes in GnomAdExome at 178 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1LW	NM_020061.6	c.532A>G	p.Ile178Val	missense_variant	3/6	ENST00000369951.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1LW	ENST00000369951.9	c.532A>G	p.Ile178Val	missense_variant	3/6	1	NM_020061.6	P1
OPN1LW	ENST00000442922.1	c.121A>G	p.Ile41Val	missense_variant	1/4	5
OPN1LW	ENST00000463296.1	n.542A>G		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0165 AC: 2708 AN: 164109 Hom.: 178 AF XY: 0.0146 AC XY: 799 AN XY: 54835

Gnomad AFR exome AF: 0.0498

Gnomad AMR exome AF: 0.0170

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.0144

Gnomad SAS exome AF: 0.0224

Gnomad FIN exome AF: 0.00860

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.0173

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.0246 Hom.: 64

ESP6500AA AF: 0.0352 AC: 134

ESP6500EA AF: 0.0132 AC: 84

ExAC AF: 0.0263 AC: 2964

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1.3% in european, 169 hemizygptes -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.0010
Dann	Benign	0.24
FATHMM_MKL	Benign	0.027	N
MetaRNN	Benign	0.0054	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.21	N;N
REVEL	Benign	0.083
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.011
MPC		0.57
ClinPred		0.0011	T
GERP RS		-5.9
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145009674; hg19: chrX-153418535; COSMIC: COSV64063910;