Genetic Variant NM_001005469.2:c.887A>G (chr11-58402523-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001005469.2(OR5B3):c.887A>G(p.Lys296Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,605,970 control chromosomes in the GnomAD database, including 99,988 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.33 ( 8304 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91684 hom. )

Consequence

OR5B3
NM_001005469.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0560

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019082725).

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.887A>G	p.Lys296Arg	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.887A>G	p.Lys296Arg	missense_variant	Exon 2 of 2		NM_001005469.2	ENSP00000493217.1		Q8NH48

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

49989

AN:

151916

Hom.:

8305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.304

GnomAD3 exomes

AF:

0.312

AC:

78260

AN:

251074

Hom.:

12969

AF XY:

0.313

AC XY:

42525

AN XY:

135682

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:

0.333

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.321

GnomAD4 exome

AF:

0.349

AC:

507755

AN:

1453936

Hom.:

91684

Cov.:

AF XY:

0.348

AC XY:

251674

AN XY:

723740

show subpopulations

Gnomad4 AFR exome

AF:

0.325

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:

0.335

Gnomad4 NFE exome

AF:

0.369

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.329

AC:

50004

AN:

152034

Hom.:

8304

Cov.:

AF XY:

0.325

AC XY:

24125

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.324

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.150

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.333

Gnomad4 NFE

AF:

0.362

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.350

Hom.:

18279

Bravo

AF:

0.321

TwinsUK

AF:

0.373

AC:

1382

ALSPAC

AF:

0.378

AC:

1457

ESP6500AA

AF:

0.328

AC:

1442

ESP6500EA

AF:

0.360

AC:

3093

ExAC

AF:

0.319

AC:

38693

Asia WGS

AF:

0.264

AC:

917

AN:

3478

EpiCase

AF:

0.354

EpiControl

AF:

0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.75

.;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-2.5

.;N

REVEL

Benign

0.041

Sift

Uncertain

0.020

.;D

Sift4G

Uncertain

0.0090

.;D

Polyphen

0.34

B;B

Vest4

0.044

MPC

0.040

ClinPred

0.011

GERP RS

3.9

Varity_R

0.24

gMVP

0.073

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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