X-154187988-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_000513.2(OPN1MW):c.331G>A(p.Val111Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V111A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 0 hem., cov: 5)

Exomes 𝑓: 0.00024 ( 24 hom. 47 hem. )

Failed GnomAD Quality Control

Consequence

OPN1MW
NM_000513.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 0.413

Publications

0 publications found

Variant links:

Genes affected

OPN1MW (HGNC:4206): (opsin 1, medium wave sensitive) This gene encodes for a light absorbing visual pigment of the opsin gene family. The encoded protein is called green cone photopigment or medium-wavelength sensitive opsin. Opsins are G-protein coupled receptors with seven transmembrane domains, an N-terminal extracellular domain, and a C-terminal cytoplasmic domain. The long-wavelength opsin gene and multiple copies of 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 deutanopic colorblindness. [provided by RefSeq, Mar 2009]

OPN1MW Gene-Disease associations (from GenCC):

blue cone monochromacy
Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE, NO_KNOWN Submitted by: G2P, Ambry Genetics, Orphanet
red-green color blindness
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

OPN1MW links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025576293).

BP6

Variant X-154187988-G-A is Benign according to our data. Variant chrX-154187988-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1284583.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPN1MW	NM_000513.2 link	c.331G>A	p.Val111Ile	missense_variant	Exon 2 of 6	ENST00000595290.6	NP_000504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPN1MW	ENST00000595290.6 link	c.331G>A	p.Val111Ile	missense_variant	Exon 2 of 6	1	NM_000513.2	ENSP00000472316.1		P04001
OPN1MW	ENST00000595330.1 link	n.341G>A		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.000110

AC:

AN:

45329

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00193

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000135

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000133

AC:

AN:

82601

AF XY:

0.0000469

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000244

AC:

180

AN:

736890

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

AN XY:

198136

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

7340

American (AMR)

AF:

0.0000963

AC:

AN:

20772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14181

East Asian (EAS)

AF:

0.0000896

AC:

AN:

22311

South Asian (SAS)

AF:

0.000339

AC:

AN:

23584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32375

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1503

European-Non Finnish (NFE)

AF:

0.000275

AC:

161

AN:

584575

Other (OTH)

AF:

0.000231

AC:

AN:

30249

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.373

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000110

AC:

AN:

45329

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

8039

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

5662

American (AMR)

AF:

0.00

AC:

AN:

3297

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1459

East Asian (EAS)

AF:

0.00

AC:

AN:

1298

South Asian (SAS)

AF:

0.00193

AC:

AN:

517

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2527

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000135

AC:

AN:

29544

Other (OTH)

AF:

0.00

AC:

AN:

531

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.026001), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.395

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000337

Hom.:

ExAC

AF:

0.000154

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.1

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

FATHMM_MKL

Benign

0.73

M_CAP

Benign

0.0043

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

PhyloP100

0.41

PrimateAI

Uncertain

0.55

Sift4G

Benign

0.36

Polyphen

0.049

Vest4

0.038

MVP

0.55

ClinPred

0.16

GERP RS

2.9

Varity_R

0.18

gMVP

0.39

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

X-154187988-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over