rs747829910

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005274.1(OR4A16):​c.100A>C​(p.Ile34Leu) 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 1,461,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. I34F) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR4A16
NM_001005274.1 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.53

Publications

1 publications found
Variant links:
Genes affected
OR4A16 (HGNC:15153): (olfactory receptor family 4 subfamily A member 16) 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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.026376158).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR4A16NM_001005274.1 linkc.100A>C p.Ile34Leu missense_variant Exon 1 of 1 ENST00000314721.5 NP_001005274.1 Q8NH70A0A126GW87

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR4A16ENST00000314721.5 linkc.100A>C p.Ile34Leu missense_variant Exon 1 of 1 6 NM_001005274.1 ENSP00000325128.2 Q8NH70

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000399
AC:
1
AN:
250836
AF XY:
0.00000738
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461452
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727028
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33466
American (AMR)
AF:
0.00
AC:
0
AN:
44678
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39626
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86248
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53378
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111790
Other (OTH)
AF:
0.00
AC:
0
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
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.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.19
DANN
Benign
0.65
DEOGEN2
Benign
0.0020
T
Eigen
Benign
-2.4
Eigen_PC
Benign
-2.5
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.00092
T
MetaRNN
Benign
0.026
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-0.91
N
PhyloP100
-2.5
PrimateAI
Benign
0.19
T
PROVEAN
Benign
-0.97
N
REVEL
Benign
0.026
Sift
Benign
0.35
T
Sift4G
Benign
0.89
T
Polyphen
0.0040
B
Vest4
0.064
MutPred
0.32
Loss of catalytic residue at I34 (P = 0.0593);
MVP
0.048
MPC
0.0011
ClinPred
0.085
T
GERP RS
-4.8
PromoterAI
0.0080
Neutral
Varity_R
0.081
gMVP
0.055
Mutation Taster
=98/2
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: rs747829910; hg19: chr11-55110776; API