rs745361366

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005275.2(OR4A15):​c.227C>A​(p.Ala76Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A76V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OR4A15
NM_001005275.2 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.464

Publications

0 publications found
Variant links:
Genes affected
OR4A15 (HGNC:15152): (olfactory receptor family 4 subfamily A member 15) 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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17809743).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR4A15NM_001005275.2 linkc.227C>A p.Ala76Asp missense_variant Exon 1 of 1 ENST00000641526.1 NP_001005275.2 Q8NGL6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR4A15ENST00000641526.1 linkc.227C>A p.Ala76Asp missense_variant Exon 1 of 1 NM_001005275.2 ENSP00000493060.1 A0A286YF59

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461356
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
726986
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33466
American (AMR)
AF:
0.00
AC:
0
AN:
44662
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39656
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86240
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5584
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111832
Other (OTH)
AF:
0.00
AC:
0
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome 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
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.65
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.12
T;.
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
M;.
PhyloP100
0.46
PrimateAI
Benign
0.22
T
PROVEAN
Uncertain
-2.4
N;.
REVEL
Benign
0.11
Sift
Uncertain
0.0040
D;.
Sift4G
Uncertain
0.0040
D;.
Polyphen
0.48
P;.
Vest4
0.43
MutPred
0.50
Loss of ubiquitination at K108 (P = 0.0768);.;
MVP
0.30
ClinPred
0.85
D
GERP RS
3.5
PromoterAI
0.0069
Neutral
Varity_R
0.71
gMVP
0.26
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs745361366; hg19: chr11-55135676; COSMIC: COSV59037239; API