chr11-56376164-G-A

Variant summary

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

The NM_001005204.1(OR8U1):​c.541G>A​(p.Asp181Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 58)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OR8U1
NM_001005204.1 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0590
Variant links:
Genes affected
OR8U1 (HGNC:19611): (olfactory receptor family 8 subfamily U 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=0.07738289).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR8U1NM_001005204.1 linkuse as main transcriptc.541G>A p.Asp181Asn missense_variant 1/1 ENST00000302270.1 NP_001005204.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR8U1ENST00000302270.1 linkuse as main transcriptc.541G>A p.Asp181Asn missense_variant 1/1 NM_001005204.1 ENSP00000304188 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152298
Hom.:
0
Cov.:
58
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000392
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248626
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134976
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461850
Hom.:
0
Cov.:
172
AF XY:
0.00
AC XY:
0
AN XY:
727226
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000459
AC:
7
AN:
152416
Hom.:
0
Cov.:
58
AF XY:
0.0000537
AC XY:
4
AN XY:
74534
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
ExAC
AF:
0.00000825
AC:
1

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 GeneticsDec 16, 2023The c.541G>A (p.D181N) alteration is located in exon 1 (coding exon 1) of the OR8U1 gene. This alteration results from a G to A substitution at nucleotide position 541, causing the aspartic acid (D) at amino acid position 181 to be replaced by an asparagine (N). 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
0.21
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0058
T
Eigen
Benign
-0.049
Eigen_PC
Benign
-0.083
FATHMM_MKL
Benign
0.024
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.077
T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.14
Sift
Benign
0.32
T
Sift4G
Benign
0.36
T
Polyphen
0.85
P
Vest4
0.11
MutPred
0.31
Gain of helix (P = 0.132);
MVP
0.59
MPC
0.46
ClinPred
0.38
T
GERP RS
3.9
Varity_R
0.15
gMVP
0.087

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs537232927; hg19: chr11-56143640; API