rs11229411

Variant names:

• chr11-58402869-C-T
• rs11229411
• NM_001005469.2:c.541G>A

Variant summary

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

The NM_001005469.2(OR5B3):​c.541G>A​(p.Ala181Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,610,002 control chromosomes in the GnomAD database, including 100,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8315 hom., cov: 32)
  • Exomes 𝑓: 0.35 (91819 hom.)
• Consequence: OR5B3 NM_001005469.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 37 publications found

Genes affected

OR5B3 (HGNC:8324): (olfactory receptor family 5 subfamily B 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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.009459317).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5B3	NM_001005469.2	c.541G>A	p.Ala181Thr	missense_variant	Exon 2 of 2	ENST00000641865.1	NP_001005469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5B3	ENST00000641865.1	c.541G>A	p.Ala181Thr	missense_variant	Exon 2 of 2		NM_001005469.2	ENSP00000493217.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50012 AN: 151900 Hom.: 8316 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.302

GnomAD2 exomes AF: 0.312 AC: 78226 AN: 251034 AF XY: 0.313

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.322

GnomAD4 exome AF: 0.350 AC: 509957 AN: 1457984 Hom.: 91819 Cov.: 36 AF XY: 0.348 AC XY: 252629 AN XY: 725518

African (AFR) AF: 0.326 AC: 10872 AN: 33374

American (AMR) AF: 0.230 AC: 10279 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8745 AN: 26098

East Asian (EAS) AF: 0.168 AC: 6664 AN: 39690

South Asian (SAS) AF: 0.284 AC: 24511 AN: 86200

European-Finnish (FIN) AF: 0.334 AC: 17844 AN: 53364

Middle Eastern (MID) AF: 0.313 AC: 1799 AN: 5752

European-Non Finnish (NFE) AF: 0.369 AC: 409234 AN: 1108560

Other (OTH) AF: 0.332 AC: 20009 AN: 60268

GnomAD4 genome AF: 0.329 AC: 50027 AN: 152018 Hom.: 8315 Cov.: 32 AF XY: 0.325 AC XY: 24148 AN XY: 74324

African (AFR) AF: 0.325 AC: 13460 AN: 41466

American (AMR) AF: 0.262 AC: 3994 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1201 AN: 3466

East Asian (EAS) AF: 0.150 AC: 778 AN: 5170

South Asian (SAS) AF: 0.300 AC: 1444 AN: 4820

European-Finnish (FIN) AF: 0.334 AC: 3533 AN: 10566

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24590 AN: 67966

Other (OTH) AF: 0.301 AC: 634 AN: 2108

Alfa AF: 0.348 Hom.: 31165

Bravo AF: 0.321

TwinsUK AF: 0.372 AC: 1379

ALSPAC AF: 0.379 AC: 1462

ESP6500AA AF: 0.328 AC: 1442

ESP6500EA AF: 0.360 AC: 3095

ExAC AF: 0.319 AC: 38687

Asia WGS AF: 0.264 AC: 917 AN: 3478

EpiCase AF: 0.355

EpiControl AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0098	T;T
Eigen	Benign	0.16
Eigen_PC	Benign	-0.0086
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.82	.;T
MetaRNN	Benign	0.0095	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L;L
PhyloP100		0.30
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-3.2	.;D
REVEL	Benign	0.083
Sift	Uncertain	0.0020	.;D
Sift4G	Pathogenic	0.0010	.;D
Polyphen		0.98	D;D
Vest4		0.091
MPC		0.23
ClinPred		0.023	T
GERP RS		3.0
Varity_R		0.64
gMVP		0.083
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11229411; hg19: chr11-58170342; COSMIC: COSV58676634;