rs3749977

Variant names:

• chr6-29112567-G-A
• rs3749977
• NM_001005216.4:c.677G>A

Variant summary

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

The NM_001005216.4(OR2J3):​c.677G>A​(p.Arg226Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,613,344 control chromosomes in the GnomAD database, including 60,389 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

• Frequency:
  • Genomes: 𝑓 0.34 (10281 hom., cov: 32)
  • Exomes 𝑓: 0.25 (50108 hom.)
• Consequence: OR2J3 NM_001005216.4 missense
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: -1.66
• Publications: 42 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=7.120634E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2J3	NM_001005216.4	c.677G>A	p.Arg226Gln	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.677G>A	p.Arg226Gln	missense_variant	Exon 4 of 4		NM_001005216.4	ENSP00000492961.1
OR2J3	ENST00000377169.2	c.677G>A	p.Arg226Gln	missense_variant	Exon 1 of 1	6		ENSP00000366374.1
OR2J3	ENST00000641960.1	c.677G>A	p.Arg226Gln	missense_variant	Exon 5 of 5			ENSP00000493439.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51399 AN: 151770 Hom.: 10258 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.339

GnomAD2 exomes AF: 0.293 AC: 72761 AN: 248488 AF XY: 0.294

Gnomad AFR exome AF: 0.560

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.395

Gnomad EAS exome AF: 0.231

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.279

GnomAD4 exome AF: 0.251 AC: 366660 AN: 1461452 Hom.: 50108 Cov.: 36 AF XY: 0.255 AC XY: 185712 AN XY: 727016

African (AFR) AF: 0.569 AC: 19038 AN: 33462

American (AMR) AF: 0.284 AC: 12678 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 10229 AN: 26130

East Asian (EAS) AF: 0.201 AC: 7979 AN: 39696

South Asian (SAS) AF: 0.372 AC: 32082 AN: 86248

European-Finnish (FIN) AF: 0.287 AC: 15321 AN: 53396

Middle Eastern (MID) AF: 0.345 AC: 1991 AN: 5764

European-Non Finnish (NFE) AF: 0.226 AC: 250826 AN: 1111674

Other (OTH) AF: 0.274 AC: 16516 AN: 60384

GnomAD4 genome AF: 0.339 AC: 51463 AN: 151892 Hom.: 10281 Cov.: 32 AF XY: 0.341 AC XY: 25327 AN XY: 74236

African (AFR) AF: 0.554 AC: 22902 AN: 41366

American (AMR) AF: 0.290 AC: 4423 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1312 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1167 AN: 5164

South Asian (SAS) AF: 0.361 AC: 1735 AN: 4808

European-Finnish (FIN) AF: 0.287 AC: 3032 AN: 10560

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.235 AC: 15993 AN: 67964

Other (OTH) AF: 0.336 AC: 707 AN: 2104

Alfa AF: 0.284 Hom.: 20318

Bravo AF: 0.351

TwinsUK AF: 0.222 AC: 824

ALSPAC AF: 0.229 AC: 881

ESP6500AA AF: 0.516 AC: 1332

ESP6500EA AF: 0.232 AC: 1194

ExAC AF: 0.297 AC: 35799

Asia WGS AF: 0.296 AC: 1034 AN: 3478

EpiCase AF: 0.238

EpiControl AF: 0.246

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 v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.7
DANN	Benign	0.56
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.32	.;.;T
MetaRNN	Benign	0.000071	T;T;T
MetaSVM	Benign	-0.99	T
PhyloP100		-1.7
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.60	.;.;N
REVEL	Benign	0.0070
Sift	Benign	0.56	.;.;T
Sift4G	Benign	0.73	.;.;T
Vest4		0.0070
MPC		0.13
ClinPred		0.000019	T
GERP RS		-4.1
gMVP		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs3749977; hg19: chr6-29080344; COSMIC: COSV65849059;