11-58422820-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005566.3(OR5B2):​c.442G>T​(p.Val148Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR5B2
NM_001005566.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.07
Variant links:
Genes affected
OR5B2 (HGNC:8323): (olfactory receptor family 5 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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.050242245).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR5B2NM_001005566.3 linkc.442G>T p.Val148Phe missense_variant Exon 3 of 3 ENST00000641342.2 NP_001005566.1 Q96R09

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR5B2ENST00000641342.2 linkc.442G>T p.Val148Phe missense_variant Exon 3 of 3 NM_001005566.3 ENSP00000493419.1 Q96R09
OR5B2ENST00000302581.2 linkc.442G>T p.Val148Phe missense_variant Exon 1 of 1 6 ENSP00000303076.2 Q96R09

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461558
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727066
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.442G>T (p.V148F) alteration is located in exon 1 (coding exon 1) of the OR5B2 gene. This alteration results from a G to T substitution at nucleotide position 442, causing the valine (V) at amino acid position 148 to be replaced by a phenylalanine (F). 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
0.082
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.021
DANN
Benign
0.79
DEOGEN2
Benign
0.013
T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.75
.;T
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.050
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.010
N;N
PrimateAI
Benign
0.22
T
PROVEAN
Uncertain
-3.1
.;D
REVEL
Benign
0.023
Sift
Benign
0.16
.;T
Sift4G
Benign
0.18
.;T
Polyphen
0.024
B;B
Vest4
0.10
MutPred
0.28
Loss of sheet (P = 0.437);Loss of sheet (P = 0.437);
MVP
0.048
MPC
0.0047
ClinPred
0.46
T
GERP RS
-7.5
Varity_R
0.10
gMVP
0.26

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.

Other links and lift over

dbSNP: rs759864188; hg19: chr11-58190293; API