11-55936167-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006637.1(OR5I1):ā€‹c.234C>Gā€‹(p.Asp78Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000014 ( 0 hom. )

Consequence

OR5I1
NM_006637.1 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.47
Variant links:
Genes affected
OR5I1 (HGNC:8347): (olfactory receptor family 5 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 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=0.050971).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR5I1NM_006637.1 linkuse as main transcriptc.234C>G p.Asp78Glu missense_variant 1/1 ENST00000301532.3 NP_006628.1 Q13606A0A126GVE5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR5I1ENST00000301532.3 linkuse as main transcriptc.234C>G p.Asp78Glu missense_variant 1/16 NM_006637.1 ENSP00000301532.3 Q13606

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151630
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249498
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134898
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000267
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1460380
Hom.:
0
Cov.:
33
AF XY:
0.0000110
AC XY:
8
AN XY:
726526
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000162
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151630
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74070
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000677
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

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 GeneticsMar 05, 2024The c.234C>G (p.D78E) alteration is located in exon 1 (coding exon 1) of the OR5I1 gene. This alteration results from a C to G substitution at nucleotide position 234, causing the aspartic acid (D) at amino acid position 78 to be replaced by a glutamic acid (E). 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
3.7
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0010
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.045
N
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.051
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.49
N
REVEL
Benign
0.065
Sift
Uncertain
0.015
D
Sift4G
Uncertain
0.011
D
Polyphen
0.023
B
Vest4
0.033
MutPred
0.41
Loss of ubiquitination at K82 (P = 0.1601);
MVP
0.30
MPC
0.014
ClinPred
0.081
T
GERP RS
1.9
Varity_R
0.099
gMVP
0.19

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144543203; hg19: chr11-55703643; API