Variant 6-29111978-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001005216.4(OR2J3):c.88A>C(p.Ile30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,613,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

OR2J3
NM_001005216.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.153

Variant links:

Genes affected

OR2J3 (HGNC:8261): (olfactory receptor family 2 subfamily J member 3) This gene encodes a G-protein-coupled receptor (GPCR) that functions as an olfactory receptor. Olfactory receptors interact with odorant molecules in the nose to initiate a neuronal response that triggers the perception of a smell. The protein encoded by this gene responds to cis-3-hexen-1-ol, which is released by wounded plants, including cut grass. This gene is situated in a cluster of similar olfactory-receptor coding genes on chromosome 6. [provided by RefSeq, May 2013]

OR2J3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016826212).

BP6

Variant 6-29111978-A-C is Benign according to our data. Variant chr6-29111978-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2367627.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2J3	NM_001005216.4 link	c.88A>C	p.Ile30Leu	missense_variant	4/4	ENST00000641151.2	NP_001005216.2	O76001A0A126GWT2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR2J3	ENST00000641151.2 link	c.88A>C	p.Ile30Leu	missense_variant	4/4		NM_001005216.4	ENSP00000492961.1	A0A126GWT2
OR2J3	ENST00000377169.2 link	c.88A>C	p.Ile30Leu	missense_variant	1/1	6		ENSP00000366374.1	O76001
OR2J3	ENST00000641960.1 link	c.88A>C	p.Ile30Leu	missense_variant	5/5			ENSP00000493439.1	A0A126GWT2

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000153

AC:

AN:

247588

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

134728

show subpopulations

Gnomad AFR exome

AF:

0.0000670

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000325

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000189

AC:

276

AN:

1461804

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

120

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.000218

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000237

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000590

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000205

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000158

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.5

DANN

Benign

0.24

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.60

.;.;T

M_CAP

Benign

0.00044

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

1.7

.;.;N

REVEL

Benign

0.016

Sift

Benign

1.0

.;.;T

Sift4G

Benign

1.0

.;.;T

Vest4

0.075

MVP

0.099

MPC

0.11

ClinPred

0.045

GERP RS

1.1

gMVP

0.093

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

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