chr6-29112227-A-G

Variant names:

• chr6-29112227-A-G
• rs28757581
• NM_001005216.4:c.337A>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. 13/20 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 the same amino acid substitution has been previously reported as Likely benign in 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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2J3	NM_001005216.4	c.337A>G	p.Thr113Ala	missense_variant	Exon 4 of 4	ENST00000641151.2	NP_001005216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2J3	ENST00000641151.2	c.337A>G	p.Thr113Ala	missense_variant	Exon 4 of 4		NM_001005216.4	ENSP00000492961.1
OR2J3	ENST00000377169.2	c.337A>G	p.Thr113Ala	missense_variant	Exon 1 of 1	6		ENSP00000366374.1
OR2J3	ENST00000641960.1	c.337A>G	p.Thr113Ala	missense_variant	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

Gnomad4 AFR exome AF: 0.356 AC: 11926 AN: 33474

Gnomad4 AMR exome AF: 0.173 AC: 7722 AN: 44720

Gnomad4 ASJ exome AF: 0.166 AC: 4336 AN: 26136

Gnomad4 EAS exome AF: 0.110 AC: 4370 AN: 39700

Gnomad4 SAS exome AF: 0.136 AC: 11735 AN: 86256

Gnomad4 FIN exome AF: 0.116 AC: 6191 AN: 53416

Gnomad4 NFE exome AF: 0.108 AC: 119756 AN: 1111880

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.341 AC: 0.340621 AN: 0.340621

Gnomad4 AMR AF: 0.153 AC: 0.152629 AN: 0.152629

Gnomad4 ASJ AF: 0.159 AC: 0.159366 AN: 0.159366

Gnomad4 EAS AF: 0.105 AC: 0.104948 AN: 0.104948

Gnomad4 SAS AF: 0.121 AC: 0.120954 AN: 0.120954

Gnomad4 FIN AF: 0.110 AC: 0.110168 AN: 0.110168

Gnomad4 NFE AF: 0.111 AC: 0.110616 AN: 0.110616

Gnomad4 OTH AF: 0.176 AC: 0.176136 AN: 0.176136

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

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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
LIST_S2	Benign	0.090	.;.;T
MetaRNN	Benign	0.0047	T;T;T
MetaSVM	Benign	-0.96	T
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

Publications

LitVar

Other links and lift over

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