Variant 11-124396550-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001005467.2(OR8B3):c.802G>C(p.Glu268Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 1,613,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

OR8B3
NM_001005467.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.259

Variant links:

Genes affected

OR8B3 (HGNC:8472): (olfactory receptor family 8 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]

OR8B3 links:

OR8B2 (HGNC:):

OR8B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR8B3	NM_001005467.2 linkuse as main transcript	c.802G>C	p.Glu268Gln	missense_variant	2/2	ENST00000641139.1
OR8B3	XM_017017716.2 linkuse as main transcript	c.802G>C	p.Glu268Gln	missense_variant	6/6
OR8B2	XM_017017535.3 linkuse as main transcript	c.-148+685G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR8B3	ENST00000641139.1 linkuse as main transcript	c.802G>C	p.Glu268Gln	missense_variant	2/2		NM_001005467.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000336

AC:

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000315

AC:

AN:

250446

Hom.:

AF XY:

0.000310

AC XY:

AN XY:

135498

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000618

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000464

AC:

678

AN:

1461622

Hom.:

Cov.:

AF XY:

0.000476

AC XY:

346

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000573

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000335

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000633

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000327

Hom.:

Bravo

AF:

0.000374

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000354

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000948

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2023

The c.802G>C (p.E268Q) alteration is located in exon 1 (coding exon 1) of the OR8B3 gene. This alteration results from a G to C substitution at nucleotide position 802, causing the glutamic acid (E) at amino acid position 268 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0080

T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.21

.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.5

.;N

REVEL

Benign

0.044

Sift

Uncertain

0.0020

.;D

Sift4G

Uncertain

0.033

.;D

Polyphen

0.25

B;B

Vest4

0.085

MVP

0.24

MPC

1.0

ClinPred

0.039

GERP RS

2.8

Varity_R

0.096

gMVP

0.052

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.29

Position offset: -3

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over