11-6027233-G-A

Variant summary

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

The NM_001388488.1(OR56A1):​c.460C>T​(p.Arg154Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,066 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 (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

OR56A1
NM_001388488.1 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.07
Variant links:
Genes affected
OR56A1 (HGNC:14781): (olfactory receptor family 56 subfamily A 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=0.24898383).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR56A1NM_001388488.1 linkc.460C>T p.Arg154Trp missense_variant 2/2 ENST00000641900.1 NP_001375417.1
OR56A1NM_001001917.5 linkc.460C>T p.Arg154Trp missense_variant 2/2 NP_001001917.3 Q8NGH5A0A126GVB5
LOC107984303XR_001748102.2 linkn.89+5145G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR56A1ENST00000641900.1 linkc.460C>T p.Arg154Trp missense_variant 2/2 NM_001388488.1 ENSP00000493047.1 A0A286YFC4
OR56A1ENST00000641423.1 linkc.460C>T p.Arg154Trp missense_variant 2/2 ENSP00000493266.1 A0A286YFC4
OR56A1ENST00000641938.1 linkc.460C>T p.Arg154Trp missense_variant 1/1 ENSP00000493321.1 A0A286YFC4

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000265
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251224
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000294
AC:
43
AN:
1461742
Hom.:
0
Cov.:
33
AF XY:
0.0000330
AC XY:
24
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152324
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.000289
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000127
Hom.:
0
Bravo
AF:
0.000140
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 GeneticsJun 11, 2024The c.472C>T (p.R158W) alteration is located in exon 1 (coding exon 1) of the OR56A1 gene. This alteration results from a C to T substitution at nucleotide position 472, causing the arginine (R) at amino acid position 158 to be replaced by a tryptophan (W). 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
0.27
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
16
DANN
Benign
0.89
DEOGEN2
Benign
0.18
.;.;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.036
N
LIST_S2
Uncertain
0.87
.;.;D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.25
T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Pathogenic
3.6
.;.;.;H
PrimateAI
Benign
0.19
T
PROVEAN
Pathogenic
-7.5
.;.;.;D
REVEL
Benign
0.075
Sift
Uncertain
0.0020
.;.;.;D
Sift4G
Uncertain
0.0040
.;.;.;D
Polyphen
0.27
.;.;.;B
Vest4
0.43
MVP
0.10
MPC
0.035
ClinPred
0.12
T
GERP RS
-4.9
Varity_R
0.26
gMVP
0.54

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: rs370641687; hg19: chr11-6048463; COSMIC: COSV57361716; API