rs606231244

Variant names:

• chr6-29112227-A-G
• rs28757581
• NM_001005216.4:c.337A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-29112227-A-G
• chrNT_167244.2-377847-A-G
• chrNT_113891.3-598775-A-G
• chrNT_167245.2-377829-A-G
• chrNT_167246.2-377786-A-G
• chrNT_167247.2-377966-A-G
• chrNT_167248.2-377812-A-G
• chrNT_167249.2-421591-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005216.4(OR2J3):​c.337A>G​(p.Thr113Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,613,856 control chromosomes in the GnomAD database, including 15,213 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (3266 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11947 hom.)
• Consequence: OR2J3 NM_001005216.4 missense
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 0.633
• Publications: 17 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047168434).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2J3	NM_001005216.4	MANE Select	c.337A>G	p.Thr113Ala	missense	Exon 4 of 4	NP_001005216.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2J3	ENST00000641151.2	MANE Select	c.337A>G	p.Thr113Ala	missense	Exon 4 of 4	ENSP00000492961.1
	OR2J3	ENST00000377169.2	TSL:6	c.337A>G	p.Thr113Ala	missense	Exon 1 of 1	ENSP00000366374.1
	OR2J3	ENST00000641960.1		c.337A>G	p.Thr113Ala	missense	Exon 5 of 5	ENSP00000493439.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27203 AN: 151992 Hom.: 3258 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.178

GnomAD2 exomes AF: 0.142 AC: 35484 AN: 249358 AF XY: 0.138

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.119 AC: 174437 AN: 1461746 Hom.: 11947 Cov.: 34 AF XY: 0.120 AC XY: 87069 AN XY: 727198

African (AFR) AF: 0.356 AC: 11926 AN: 33474

American (AMR) AF: 0.173 AC: 7722 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4336 AN: 26136

East Asian (EAS) AF: 0.110 AC: 4370 AN: 39700

South Asian (SAS) AF: 0.136 AC: 11735 AN: 86256

European-Finnish (FIN) AF: 0.116 AC: 6191 AN: 53416

Middle Eastern (MID) AF: 0.149 AC: 861 AN: 5768

European-Non Finnish (NFE) AF: 0.108 AC: 119756 AN: 1111880

Other (OTH) AF: 0.125 AC: 7540 AN: 60396

GnomAD4 genome AF: 0.179 AC: 27253 AN: 152110 Hom.: 3266 Cov.: 32 AF XY: 0.178 AC XY: 13205 AN XY: 74388

African (AFR) AF: 0.341 AC: 14116 AN: 41442

American (AMR) AF: 0.153 AC: 2334 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3470

East Asian (EAS) AF: 0.105 AC: 543 AN: 5174

South Asian (SAS) AF: 0.121 AC: 583 AN: 4820

European-Finnish (FIN) AF: 0.110 AC: 1168 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7521 AN: 67992

Other (OTH) AF: 0.176 AC: 372 AN: 2112

Alfa AF: 0.145 Hom.: 1295

Bravo AF: 0.195

TwinsUK AF: 0.108 AC: 401

ALSPAC AF: 0.108 AC: 417

ESP6500AA AF: 0.297 AC: 809

ESP6500EA AF: 0.108 AC: 569

ExAC AF: 0.144 AC: 17479

EpiCase AF: 0.107

EpiControl AF: 0.116

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

C3HEX, ability to smell Other:1

Sep 01, 2012

OMIM

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.96
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.090	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.63
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.019
Sift	Benign	0.078	T
Sift4G	Benign	0.093	T
Vest4		0.043
MPC		0.13
ClinPred		0.0062	T
GERP RS		2.8
gMVP		0.11
Mutation Taster		=99/1	polymorphism (auto)

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: rs28757581; hg19: chr6-29080004; COSMIC: COSV65849055;