chr11-124310296-C-A

Variant summary

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

The NM_001002917.2(OR8D1):​c.471G>T​(p.Leu157Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

OR8D1
NM_001002917.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.06
Variant links:
Genes affected
OR8D1 (HGNC:8481): (olfactory receptor family 8 subfamily D 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=0.011552632).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR8D1NM_001002917.2 linkc.471G>T p.Leu157Phe missense_variant 3/3 ENST00000641015.1 NP_001002917.1 Q8WZ84A0A126GVG6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR8D1ENST00000641015.1 linkc.471G>T p.Leu157Phe missense_variant 3/3 NM_001002917.2 ENSP00000493365.1 Q8WZ84
OR8D1ENST00000357821.2 linkc.471G>T p.Leu157Phe missense_variant 1/16 ENSP00000350474.2 Q8WZ84
OR8D1ENST00000641897.1 linkc.471G>T p.Leu157Phe missense_variant 4/4 ENSP00000493091.1 Q8WZ84

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152026
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000852
Gnomad ASJ
AF:
0.00289
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000192
AC:
48
AN:
250642
Hom.:
0
AF XY:
0.000148
AC XY:
20
AN XY:
135460
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000870
Gnomad ASJ exome
AF:
0.00149
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000650
AC:
95
AN:
1461538
Hom.:
0
Cov.:
37
AF XY:
0.0000523
AC XY:
38
AN XY:
727060
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000783
Gnomad4 ASJ exome
AF:
0.00134
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000851
Gnomad4 ASJ
AF:
0.00289
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000262
Hom.:
0
Bravo
AF:
0.000178
ExAC
AF:
0.000132
AC:
16
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

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 07, 2024The c.471G>T (p.L157F) alteration is located in exon 1 (coding exon 1) of the OR8D1 gene. This alteration results from a G to T substitution at nucleotide position 471, causing the leucine (L) at amino acid position 157 to be replaced by a phenylalanine (F). 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
0.086
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
1.7
DANN
Benign
0.96
DEOGEN2
Benign
0.0062
T;T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.65
.;.;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.012
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;L;L
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-1.4
.;.;N
REVEL
Benign
0.010
Sift
Benign
0.059
.;.;T
Sift4G
Benign
0.13
.;.;T
Polyphen
0.014
B;B;B
Vest4
0.043
MutPred
0.31
Loss of stability (P = 0.1158);Loss of stability (P = 0.1158);Loss of stability (P = 0.1158);
MVP
0.055
MPC
0.034
ClinPred
0.030
T
GERP RS
-0.81
Varity_R
0.055
gMVP
0.053

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: rs192131391; hg19: chr11-124180192; API