11-124396840-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001005467.2(OR8B3):​c.512C>T​(p.Ala171Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 30)

Consequence

OR8B3
NM_001005467.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0570
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058714956).
BP6
Variant 11-124396840-G-A is Benign according to our data. Variant chr11-124396840-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3303411.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR8B3NM_001005467.2 linkuse as main transcriptc.512C>T p.Ala171Val missense_variant 2/2 ENST00000641139.1 NP_001005467.1 Q8NGG8
OR8B3XM_017017716.2 linkuse as main transcriptc.512C>T p.Ala171Val missense_variant 6/6 XP_016873205.1 Q8NGG8
OR8B2XM_017017535.3 linkuse as main transcriptc.-148+395C>T intron_variant XP_016873024.1 Q96RD0A0A126GVQ4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR8B3ENST00000641139.1 linkuse as main transcriptc.512C>T p.Ala171Val missense_variant 2/2 NM_001005467.2 ENSP00000493120.1 Q8NGG8

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMar 28, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
11
DANN
Benign
0.92
DEOGEN2
Benign
0.0088
T;T
Eigen
Benign
-0.97
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.053
N
LIST_S2
Benign
0.23
.;T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.059
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-2.1
.;N
REVEL
Benign
0.016
Sift
Benign
0.17
.;T
Sift4G
Benign
0.21
.;T
Polyphen
0.0020
B;B
Vest4
0.045
MutPred
0.24
Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP
0.32
MPC
0.55
ClinPred
0.64
D
GERP RS
-1.1
Varity_R
0.034
gMVP
0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-124266736; COSMIC: COSV63541820; API