chr9-122510832-G-A

Variant names:

• chr9-122510832-G-A
• rs1350861546
• NM_054107.1:c.31G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_054107.1(OR1J2):​c.31G>A​(p.Glu11Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,601,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: OR1J2 NM_054107.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00200
• Publications: 1 publications found

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]

ENSG00000234156 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07565692).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054107.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1J2	NM_054107.1	MANE Select	c.31G>A	p.Glu11Lys	missense	Exon 1 of 1	NP_473448.1	Q8NGS2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1J2	ENST00000335302.5	TSL:6 MANE Select	c.31G>A	p.Glu11Lys	missense	Exon 1 of 1	ENSP00000335575.5	Q8NGS2
	ENSG00000234156	ENST00000431442.3	TSL:3	n.1362+7962G>A		intron	N/A
	ENSG00000234156	ENST00000723589.1		n.1044+41647G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152134 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000203 AC: 5 AN: 246456 AF XY: 0.0000225

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000145 AC: 21 AN: 1449680 Hom.: 0 Cov.: 30 AF XY: 0.00000555 AC XY: 4 AN XY: 720728

African (AFR) AF: 0.0000601 AC: 2 AN: 33254

American (AMR) AF: 0.00 AC: 0 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25612

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39600

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102908

Other (OTH) AF: 0.000117 AC: 7 AN: 59930

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152134 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.0020
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.072
Sift	Benign	0.043	D
Sift4G	Benign	0.063	T
Polyphen		0.057	B
Vest4		0.081
MutPred		0.55		Gain of methylation at E11 (P = 0.0036)
MVP		0.29
MPC		0.019
ClinPred		0.11	T
GERP RS		0.70
PromoterAI		0.018	Neutral
Varity_R		0.15
gMVP		0.31
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1350861546; hg19: chr9-125273111; COSMIC: COSV104647198;