NM_012378.2:c.283G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012378.2(OR8B8):​c.283G>A​(p.Ala95Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,614,132 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

OR8B8
NM_012378.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.20

Publications

6 publications found
Variant links:
Genes affected
OR8B8 (HGNC:8477): (olfactory receptor family 8 subfamily B member 8) 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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.010525972).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR8B8NM_012378.2 linkc.283G>A p.Ala95Thr missense_variant Exon 3 of 3 ENST00000642064.1 NP_036510.1 Q15620A0A126GW73

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR8B8ENST00000642064.1 linkc.283G>A p.Ala95Thr missense_variant Exon 3 of 3 NM_012378.2 ENSP00000493014.1 Q15620
OR8B8ENST00000328064.2 linkc.283G>A p.Ala95Thr missense_variant Exon 1 of 1 6 ENSP00000330280.2 Q15620

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.000131
AC:
33
AN:
251312
AF XY:
0.000184
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000238
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000215
AC:
315
AN:
1461884
Hom.:
1
Cov.:
33
AF XY:
0.000232
AC XY:
169
AN XY:
727242
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000756
AC:
3
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.0000374
AC:
2
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.000272
AC:
302
AN:
1112004
Other (OTH)
AF:
0.000132
AC:
8
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.473
Heterozygous variant carriers
0
17
34
51
68
85
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152248
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74436
show subpopulations
African (AFR)
AF:
0.0000481
AC:
2
AN:
41544
American (AMR)
AF:
0.0000653
AC:
1
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.000194
AC:
1
AN:
5162
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.0000943
AC:
1
AN:
10604
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.000206
AC:
14
AN:
68020
Other (OTH)
AF:
0.000473
AC:
1
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.480
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000221
Hom.:
0
Bravo
AF:
0.000159
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000165
AC:
20
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 16, 2021
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.283G>A (p.A95T) alteration is located in exon 1 (coding exon 1) of the OR8B8 gene. This alteration results from a G to A substitution at nucleotide position 283, causing the alanine (A) at amino acid position 95 to be replaced by a threonine (T). 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
0.079
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
3.6
DANN
Benign
0.80
DEOGEN2
Benign
0.0065
T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.045
N
LIST_S2
Benign
0.16
.;T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.011
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.46
N;N
PhyloP100
-3.2
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-0.24
.;N
REVEL
Benign
0.0070
Sift
Benign
0.59
.;T
Sift4G
Benign
0.74
.;T
Polyphen
0.0030
B;B
Vest4
0.069
MVP
0.20
MPC
0.016
ClinPred
0.021
T
GERP RS
-1.4
PromoterAI
-0.094
Neutral
Varity_R
0.040
gMVP
0.060
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs186680261; hg19: chr11-124310699; COSMIC: COSV60145407; API