11-6921495-G-C

Variant names:

• chr11-6921495-G-C
• rs10839659
• NM_001004684.1:c.494G>C

Variant summary

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

The NM_001004684.1(OR2D3):​c.494G>C​(p.Trp165Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,613,616 control chromosomes in the GnomAD database, including 106,548 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (7719 hom., cov: 31)
  • Exomes 𝑓: 0.36 (98829 hom.)
• Consequence: OR2D3 NM_001004684.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.946
• Publications: 33 publications found

Genes affected

OR2D3 (HGNC:15146): (olfactory receptor family 2 subfamily D 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]

ENSG00000283415 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.008474678).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004684.1. 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
	OR2D3	NM_001004684.1	MANE Select	c.494G>C	p.Trp165Ser	missense	Exon 1 of 1	NP_001004684.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2D3	ENST00000317834.5	TSL:6 MANE Select	c.494G>C	p.Trp165Ser	missense	Exon 1 of 1	ENSP00000320560.3
	ENSG00000283415	ENST00000637205.2	TSL:5	n.605+3003C>G		intron	N/A
	ENSG00000283415	ENST00000767881.1		n.214+3003C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44515 AN: 151910 Hom.: 7723 Cov.: 31

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.333

GnomAD2 exomes AF: 0.338 AC: 84913 AN: 251030 AF XY: 0.346

Gnomad AFR exome AF: 0.0842

Gnomad AMR exome AF: 0.295

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.354

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.383

Gnomad OTH exome AF: 0.364

GnomAD4 exome AF: 0.364 AC: 532038 AN: 1461588 Hom.: 98829 Cov.: 58 AF XY: 0.364 AC XY: 264990 AN XY: 727096

African (AFR) AF: 0.0820 AC: 2746 AN: 33476

American (AMR) AF: 0.297 AC: 13273 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 9073 AN: 26118

East Asian (EAS) AF: 0.332 AC: 13163 AN: 39700

South Asian (SAS) AF: 0.317 AC: 27299 AN: 86206

European-Finnish (FIN) AF: 0.362 AC: 19330 AN: 53392

Middle Eastern (MID) AF: 0.330 AC: 1901 AN: 5766

European-Non Finnish (NFE) AF: 0.382 AC: 424268 AN: 1111840

Other (OTH) AF: 0.348 AC: 20985 AN: 60386

GnomAD4 genome AF: 0.293 AC: 44511 AN: 152028 Hom.: 7719 Cov.: 31 AF XY: 0.294 AC XY: 21835 AN XY: 74292

African (AFR) AF: 0.0927 AC: 3845 AN: 41478

American (AMR) AF: 0.328 AC: 5010 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3472

East Asian (EAS) AF: 0.355 AC: 1832 AN: 5160

South Asian (SAS) AF: 0.321 AC: 1545 AN: 4814

European-Finnish (FIN) AF: 0.369 AC: 3895 AN: 10542

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26095 AN: 67986

Other (OTH) AF: 0.333 AC: 702 AN: 2106

Alfa AF: 0.368 Hom.: 8067

Bravo AF: 0.279

TwinsUK AF: 0.369 AC: 1370

ALSPAC AF: 0.380 AC: 1463

ESP6500AA AF: 0.103 AC: 454

ESP6500EA AF: 0.374 AC: 3214

ExAC AF: 0.334 AC: 40561

EpiCase AF: 0.386

EpiControl AF: 0.386

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0085	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.95
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-13	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.20
MPC		0.21
ClinPred		0.083	T
GERP RS		5.2
PromoterAI		0.011	Neutral
Varity_R		0.94
gMVP		0.64
Mutation Taster		=77/23	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10839659; hg19: chr11-6942726; COSMIC: COSV53492238; COSMIC: COSV53492238;