Variant rs11229413 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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 same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
OR5B3	NM_001005469.2 linkuse as main transcript	c.145T>C	p.Trp49Arg	missense_variant	2/2	ENST00000641865.1	NP_001005469.1	Q8NH48A0A126GVH3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5B3	ENST00000641865.1 linkuse as main transcript	c.145T>C	p.Trp49Arg	missense_variant	2/2		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

GnomAD3 exomes

AF:

0.312

AC:

78149

AN:

250808

Hom.:

12953

AF XY:

0.313

AC XY:

42489

AN XY:

135594

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 SAS exome

AF:

0.285

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

Gnomad4 AFR exome

AF:

0.326

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.335

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.334

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.329

AC:

49973

AN:

151994

Hom.:

8296

Cov.:

AF XY:

0.325

AC XY:

24109

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.324

Gnomad4 AMR

AF:

0.261

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.150

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.362

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.350

Hom.:

23623

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over