Variant chr9-122511114-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_054107.1(OR1J2):c.313A>T(p.Ile105Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 974,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

OR1J2
NM_054107.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.58

Variant links:

Genes affected

OR1J2 (HGNC:8209): (olfactory receptor family 1 subfamily J member 2) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR1J2 links:

ENSG00000234156 (HGNC:):

ENSG00000234156 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019889742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR1J2	NM_054107.1 link	c.313A>T	p.Ile105Leu	missense_variant	1/1	ENST00000335302.5	NP_473448.1	Q8NGS2A0A126GW18
OR1J2	XM_024447516.2 link	c.313A>T	p.Ile105Leu	missense_variant	3/3		XP_024303284.1
OR1J2	XM_024447517.2 link	c.313A>T	p.Ile105Leu	missense_variant	4/4		XP_024303285.1
OR1J2	XR_007061271.1 link	n.1540+8244A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR1J2	ENST00000335302.5 link	c.313A>T	p.Ile105Leu	missense_variant	1/1	6	NM_054107.1	ENSP00000335575.5		Q8NGS2
ENSG00000234156	ENST00000431442.2 link	n.1362+8244A>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000157

AC:

AN:

190768

Hom.:

AF XY:

0.0000199

AC XY:

AN XY:

100458

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000121

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000182

AC:

AN:

823396

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

423456

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000547

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000213

Gnomad4 OTH exome

AF:

0.0000261

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151232

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73844

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2022

The c.313A>T (p.I105L) alteration is located in exon 1 (coding exon 1) of the OR1J2 gene. This alteration results from a A to T substitution at nucleotide position 313, causing the isoleucine (I) at amino acid position 105 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.034

DANN

Benign

0.49

DEOGEN2

Benign

0.0031

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.18

M_CAP

Benign

0.0011

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.40

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.16

REVEL

Benign

0.030

Sift

Benign

0.86

Sift4G

Benign

0.81

Polyphen

0.0

Vest4

0.12

MutPred

0.32

Loss of catalytic residue at L110 (P = 0.0226);

MVP

0.30

MPC

0.017

ClinPred

0.035

GERP RS

-4.8

Varity_R

0.090

gMVP

0.063

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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