rs606231244

chr6-29112227-A-GchrNT_167244.2-377846-A-GchrNT_113891.3-598774-A-GchrNT_167245.2-377828-A-GchrNT_167246.2-377785-A-GchrNT_167247.2-377965-A-GchrNT_167248.2-377811-A-GchrNT_167249.2-421590-A-G

Variant summary

Our verdict is Benign. Variant got -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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2J3	NM_001005216.4	c.337A>G	p.Thr113Ala	missense_variant	4/4	ENST00000641151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2J3	ENST00000641151.2	c.337A>G	p.Thr113Ala	missense_variant	4/4		NM_001005216.4	P1
OR2J3	ENST00000377169.2	c.337A>G	p.Thr113Ala	missense_variant	1/1			P1
OR2J3	ENST00000641960.1	c.337A>G	p.Thr113Ala	missense_variant	5/5			P1

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

GnomAD3 exomes AF: 0.142 AC: 35484 AN: 249358 Hom.: 3088 AF XY: 0.138 AC XY: 18647 AN XY: 135316

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 SAS exome AF: 0.137

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

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.110

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.125

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

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.176

Alfa AF: 0.144 Hom.: 924

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

Affects, no assertion criteria provided

literature only

OMIM

Sep 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

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
MetaRNN	Benign	0.0047	T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
Vest4		0.043
MPC		0.13
ClinPred		0.0062	T
GERP RS		2.8
gMVP		0.11

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

Other links and lift over

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