chr19-15087939-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004713.2(OR1I1):ā€‹c.874A>Gā€‹(p.Ile292Val) 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 1,461,748 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 (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I292T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

OR1I1
NM_001004713.2 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.411
Variant links:
Genes affected
OR1I1 (HGNC:8207): (olfactory receptor family 1 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07983312).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OR1I1NM_001004713.2 linkuse as main transcriptc.874A>G p.Ile292Val missense_variant 2/2 ENST00000641398.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OR1I1ENST00000641398.1 linkuse as main transcriptc.874A>G p.Ile292Val missense_variant 2/2 NM_001004713.2 P1
OR1I1ENST00000209540.2 linkuse as main transcriptc.874A>G p.Ile292Val missense_variant 1/1 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461748
Hom.:
0
Cov.:
65
AF XY:
0.00000138
AC XY:
1
AN XY:
727170
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsMay 15, 2024The c.874A>G (p.I292V) alteration is located in exon 1 (coding exon 1) of the OR1I1 gene. This alteration results from a A to G substitution at nucleotide position 874, causing the isoleucine (I) at amino acid position 292 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0047
T;T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.55
.;T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.080
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-0.78
.;N
REVEL
Benign
0.064
Sift
Uncertain
0.0010
.;D
Sift4G
Pathogenic
0.0010
.;D
Polyphen
0.0
B;B
Vest4
0.060
MutPred
0.50
Gain of MoRF binding (P = 0.1152);Gain of MoRF binding (P = 0.1152);
MVP
0.092
MPC
0.038
ClinPred
0.13
T
GERP RS
3.6
Varity_R
0.20
gMVP
0.084

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-15198750; API