dbSNP rs11229413: OR5B3:p.Trp49Arg (chr11-58403265-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001005469.2(OR5B3):c.145T>C(p.Trp49Arg) 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 1,612,706 control chromosomes in the GnomAD database, including 100,122 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 ( 8296 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91826 hom. )

Consequence

OR5B3
NM_001005469.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.71

Publications

31 publications found

Variant links:

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]

OR5B3 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.003997773).

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 link	c.145T>C	p.Trp49Arg	missense_variant	Exon 2 of 2	ENST00000641865.1	NP_001005469.1	Q8NH48A0A126GVH3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5B3	ENST00000641865.1 link	c.145T>C	p.Trp49Arg	missense_variant	Exon 2 of 2		NM_001005469.2	ENSP00000493217.1		Q8NH48

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

49958

AN:

151876

Hom.:

8297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.304

GnomAD2 exomes

AF:

0.312

AC:

78149

AN:

250808

AF XY:

0.313

show subpopulations

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:

511335

AN:

1460712

Hom.:

91826

Cov.:

AF XY:

0.348

AC XY:

253250

AN XY:

726726

show subpopulations

African (AFR)

AF:

0.326

AC:

10910

AN:

33448

American (AMR)

AF:

0.230

AC:

10279

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

8750

AN:

26110

East Asian (EAS)

AF:

0.168

AC:

6667

AN:

39696

South Asian (SAS)

AF:

0.284

AC:

24521

AN:

86224

European-Finnish (FIN)

AF:

0.334

AC:

17851

AN:

53386

Middle Eastern (MID)

AF:

0.313

AC:

1803

AN:

5762

European-Non Finnish (NFE)

AF:

0.369

AC:

410490

AN:

1111038

Other (OTH)

AF:

0.332

AC:

20064

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

16243

32487

48730

64974

81217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.329

AC:

49973

AN:

151994

Hom.:

8296

Cov.:

AF XY:

0.325

AC XY:

24109

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.324

AC:

13419

AN:

41418

American (AMR)

AF:

0.261

AC:

3991

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1201

AN:

3470

East Asian (EAS)

AF:

0.150

AC:

778

AN:

5176

South Asian (SAS)

AF:

0.299

AC:

1438

AN:

4810

European-Finnish (FIN)

AF:

0.334

AC:

3528

AN:

10574

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.362

AC:

24583

AN:

67964

Other (OTH)

AF:

0.302

AC:

638

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1714

3428

5143

6857

8571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.347

Hom.:

32266

Bravo

AF:

0.321

TwinsUK

AF:

0.373

AC:

1382

ALSPAC

AF:

0.380

AC:

1463

ESP6500AA

AF:

0.328

AC:

1443

ESP6500EA

AF:

0.360

AC:

3094

ExAC

AF:

0.319

AC:

38675

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

0.12

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.5

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.21

.;T

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.73

N;N

PhyloP100

-3.7

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-3.2

.;D

REVEL

Benign

0.11

Sift

Uncertain

0.015

.;D

Sift4G

Benign

0.11

.;T

Polyphen

0.073

B;B

Vest4

0.036

MutPred

0.14

Gain of methylation at W49 (P = 0.0537);Gain of methylation at W49 (P = 0.0537);

MPC

0.042

ClinPred

0.045

GERP RS

-8.4

Varity_R

0.24

gMVP

0.049

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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rs11229413

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over