11-5047201-G-A

Position:

• chr11-5047201-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001916.2(OR52J3):​c.676G>A​(p.Val226Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,610,390 control chromosomes in the GnomAD database, including 32,853 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.21 (3584 hom., cov: 26)
  • Exomes 𝑓: 0.20 (29269 hom.)
• Consequence: OR52J3 NM_001001916.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

Genes affected

OR52J3 (HGNC:14799): (olfactory receptor family 52 subfamily J member 3) 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062103868).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52J3	NM_001001916.2	c.676G>A	p.Val226Ile	missense_variant	1/1	ENST00000380370.1	NP_001001916.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52J3	ENST00000380370.1	c.676G>A	p.Val226Ile	missense_variant	1/1	6	NM_001001916.2	ENSP00000369728.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 31553 AN: 148564 Hom.: 3576 Cov.: 26

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.226

GnomAD3 exomes AF: 0.216 AC: 54301 AN: 251232 Hom.: 6496 AF XY: 0.214 AC XY: 29053 AN XY: 135770

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.124

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.196 AC: 286561 AN: 1461708 Hom.: 29269 Cov.: 43 AF XY: 0.198 AC XY: 143716 AN XY: 727148

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.212 AC: 31594 AN: 148682 Hom.: 3584 Cov.: 26 AF XY: 0.213 AC XY: 15405 AN XY: 72256

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.224

Alfa AF: 0.194 Hom.: 6354

Bravo AF: 0.226

TwinsUK AF: 0.177 AC: 655

ALSPAC AF: 0.183 AC: 705

ESP6500AA AF: 0.245 AC: 1079

ESP6500EA AF: 0.187 AC: 1605

ExAC AF: 0.211 AC: 25639

Asia WGS AF: 0.179 AC: 622 AN: 3478

EpiCase AF: 0.183

EpiControl AF: 0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.078
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.046
Sift	Benign	0.033	D
Sift4G	Uncertain	0.046	D
Polyphen		0.98	D
Vest4		0.035
MPC		0.016
ClinPred		0.011	T
GERP RS		3.3
Varity_R		0.087
gMVP		0.049

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: rs17350764; hg19: chr11-5068431; COSMIC: COSV66746780;