11-58118969-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001005211.2(OR9I1):c.476G>A(p.Arg159His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 0 hom. )
Consequence
OR9I1
NM_001005211.2 missense
NM_001005211.2 missense
Scores
14
Clinical Significance
Conservation
PhyloP100: -1.42
Genes affected
OR9I1 (HGNC:14718): (olfactory receptor family 9 subfamily I member 1) 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]
OR9Q1 (HGNC:14724): (olfactory receptor family 9 subfamily Q member 1) 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 -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.01055631).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| OR9I1 | NM_001005211.2 | c.476G>A | p.Arg159His | missense_variant | 3/3 | ENST00000641439.1 | |
| OR9Q1 | NM_001005212.4 | c.-14-60462C>T | intron_variant | ENST00000335397.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| OR9I1 | ENST00000641439.1 | c.476G>A | p.Arg159His | missense_variant | 3/3 | NM_001005211.2 | P1 | ||
| OR9Q1 | ENST00000335397.3 | c.-14-60462C>T | intron_variant | NM_001005212.4 | P1 | ||||
| OR9I1 | ENST00000641478.1 | c.476G>A | p.Arg159His | missense_variant | 3/3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000421 AC: 64AN: 152104Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.000367 AC: 92AN: 250358Hom.: 0 AF XY: 0.000362 AC XY: 49AN XY: 135328
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GnomAD4 exome AF: 0.000320 AC: 467AN: 1461600Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 244AN XY: 727108
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GnomAD4 genome ? AF: 0.000420 AC: 64AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74432
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2022 | The c.476G>A (p.R159H) alteration is located in exon 1 (coding exon 1) of the OR9I1 gene. This alteration results from a G to A substitution at nucleotide position 476, causing the arginine (R) at amino acid position 159 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N
MutationTaster
Benign
N;N
PrimateAI
Benign
T
Polyphen
B;B;B
Vest4
0.14
MVP
0.043
MPC
0.021
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at