17-3397984-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003553.3(OR1E1):​c.427G>A​(p.Ala143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,613,398 control chromosomes in the GnomAD database, including 714 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.021 ( 64 hom., cov: 32)
Exomes 𝑓: 0.028 ( 650 hom. )

Consequence

OR1E1
NM_003553.3 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.00
Variant links:
Genes affected
OR1E1 (HGNC:8189): (olfactory receptor family 1 subfamily E 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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.012420684).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0208 (3159/151684) while in subpopulation NFE AF= 0.0322 (2189/68000). AF 95% confidence interval is 0.0311. There are 64 homozygotes in gnomad4. There are 1378 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR1E1NM_003553.3 linkc.427G>A p.Ala143Thr missense_variant 1/1 ENST00000322608.2 NP_003544.2 P30953

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR1E1ENST00000322608.2 linkc.427G>A p.Ala143Thr missense_variant 1/16 NM_003553.3 ENSP00000313384.2 P30953

Frequencies

GnomAD3 genomes
AF:
0.0208
AC:
3159
AN:
151568
Hom.:
64
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00665
Gnomad AMI
AF:
0.152
Gnomad AMR
AF:
0.0166
Gnomad ASJ
AF:
0.00778
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00540
Gnomad FIN
AF:
0.0185
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.0322
Gnomad OTH
AF:
0.0225
GnomAD3 exomes
AF:
0.0208
AC:
5228
AN:
251100
Hom.:
73
AF XY:
0.0215
AC XY:
2922
AN XY:
135770
show subpopulations
Gnomad AFR exome
AF:
0.00602
Gnomad AMR exome
AF:
0.0138
Gnomad ASJ exome
AF:
0.00714
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00487
Gnomad FIN exome
AF:
0.0220
Gnomad NFE exome
AF:
0.0334
Gnomad OTH exome
AF:
0.0258
GnomAD4 exome
AF:
0.0280
AC:
40996
AN:
1461714
Hom.:
650
Cov.:
31
AF XY:
0.0275
AC XY:
20009
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.00492
Gnomad4 AMR exome
AF:
0.0152
Gnomad4 ASJ exome
AF:
0.00704
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00509
Gnomad4 FIN exome
AF:
0.0212
Gnomad4 NFE exome
AF:
0.0332
Gnomad4 OTH exome
AF:
0.0233
GnomAD4 genome
AF:
0.0208
AC:
3159
AN:
151684
Hom.:
64
Cov.:
32
AF XY:
0.0186
AC XY:
1378
AN XY:
74172
show subpopulations
Gnomad4 AFR
AF:
0.00663
Gnomad4 AMR
AF:
0.0166
Gnomad4 ASJ
AF:
0.00778
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00540
Gnomad4 FIN
AF:
0.0185
Gnomad4 NFE
AF:
0.0322
Gnomad4 OTH
AF:
0.0222
Alfa
AF:
0.0158
Hom.:
4
Bravo
AF:
0.0210
TwinsUK
AF:
0.0345
AC:
128
ALSPAC
AF:
0.0278
AC:
107
ESP6500AA
AF:
0.00658
AC:
29
ESP6500EA
AF:
0.0329
AC:
283
ExAC
AF:
0.0215
AC:
2609
EpiCase
AF:
0.0335
EpiControl
AF:
0.0339

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.79
T
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.057
DANN
Benign
0.94
DEOGEN2
Benign
0.015
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0015
N
LIST_S2
Benign
0.21
T
MetaRNN
Benign
0.012
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.18
N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.22
N
REVEL
Benign
0.055
Sift
Benign
0.088
T
Sift4G
Uncertain
0.026
D
Polyphen
0.013
B
Vest4
0.0060
MPC
0.32
ClinPred
0.013
T
GERP RS
-2.3
Varity_R
0.041
gMVP
0.077

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: rs150989; hg19: chr17-3301278; COSMIC: COSV59459076; API