dbSNP rs145009674: OPN1LW:p.Ile178Val (chrX-154153062-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.68

Variant links:

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]

OPN1LW links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005366087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPN1LW	NM_020061.6 link	c.532A>G	p.Ile178Val	missense_variant	Exon 3 of 6	ENST00000369951.9	NP_064445.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OPN1LW	ENST00000369951.9 link	c.532A>G	p.Ile178Val	missense_variant	Exon 3 of 6	1	NM_020061.6	ENSP00000358967.4	P04000
OPN1LW	ENST00000442922.1 link	c.121A>G	p.Ile41Val	missense_variant	Exon 1 of 4	5		ENSP00000402493.1	H0Y622
OPN1LW	ENST00000463296.1 link	n.542A>G		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0165

AC:

2708

AN:

164109

Hom.:

178

AF XY:

0.0146

AC XY:

799

AN XY:

54835

show subpopulations

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.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0246

Hom.:

ESP6500AA

AF:

0.0352

AC:

134

ESP6500EA

AF:

0.0132

AC:

ExAC

AF:

0.0263

AC:

2964

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0010

DANN

Benign

0.24

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.66

.;T

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.39

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over