11-124382845-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005468.2(OR8B2):ā€‹c.499A>Cā€‹(p.Thr167Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000998 in 1,603,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000060 ( 0 hom., cov: 29)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

OR8B2
NM_001005468.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0190
Variant links:
Genes affected
OR8B2 (HGNC:8471): (olfactory receptor family 8 subfamily B member 2) 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16617495).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR8B2NM_001005468.2 linkuse as main transcriptc.499A>C p.Thr167Pro missense_variant 2/2 ENST00000641451.2 NP_001005468.1 Q96RD0A0A126GVQ4
OR8B2XM_017017535.3 linkuse as main transcriptc.499A>C p.Thr167Pro missense_variant 3/3 XP_016873024.1 Q96RD0A0A126GVQ4
OR8B2XM_017017536.2 linkuse as main transcriptc.499A>C p.Thr167Pro missense_variant 3/3 XP_016873025.1 Q96RD0A0A126GVQ4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR8B2ENST00000641451.2 linkuse as main transcriptc.499A>C p.Thr167Pro missense_variant 2/2 NM_001005468.2 ENSP00000493235.1 Q96RD0

Frequencies

GnomAD3 genomes
AF:
0.0000595
AC:
9
AN:
151238
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.000219
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000165
AC:
4
AN:
242084
Hom.:
0
AF XY:
0.00000764
AC XY:
1
AN XY:
130838
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.0000598
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000482
AC:
7
AN:
1452716
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
722804
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.0000452
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000595
AC:
9
AN:
151238
Hom.:
0
Cov.:
29
AF XY:
0.0000542
AC XY:
4
AN XY:
73772
show subpopulations
Gnomad4 AFR
AF:
0.000219
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000529
ExAC
AF:
0.0000330
AC:
4

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 submitterclinical testingAmbry GeneticsFeb 09, 2023The c.499A>C (p.T167P) alteration is located in exon 1 (coding exon 1) of the OR8B2 gene. This alteration results from a A to C substitution at nucleotide position 499, causing the threonine (T) at amino acid position 167 to be replaced by a proline (P). 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
0.075
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.53
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0070
T;T
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.40
.;T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
-1.5
N;N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-3.9
.;D
REVEL
Benign
0.075
Sift
Uncertain
0.0030
.;D
Sift4G
Benign
0.14
.;T
Polyphen
1.0
D;D
Vest4
0.14
MVP
0.28
MPC
1.3
ClinPred
0.30
T
GERP RS
2.8
Varity_R
0.27
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs745901199; hg19: chr11-124252741; API