17-58156079-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001386095.1(OR4D1):​c.926G>A​(p.Arg309Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,584,546 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

OR4D1
NM_001386095.1 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.200
Variant links:
Genes affected
OR4D1 (HGNC:8293): (olfactory receptor family 4 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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.016564429).
BP6
Variant 17-58156079-G-A is Benign according to our data. Variant chr17-58156079-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2370982.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR4D1NM_001386095.1 linkc.926G>A p.Arg309Lys missense_variant 4/4 ENST00000268912.6 NP_001373024.1
OR4D1NM_012374.2 linkc.926G>A p.Arg309Lys missense_variant 3/3 NP_036506.1 Q15615

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR4D1ENST00000268912.6 linkc.926G>A p.Arg309Lys missense_variant 4/46 NM_001386095.1 ENSP00000365451.3 Q15615
OR4D1ENST00000641449.1 linkc.926G>A p.Arg309Lys missense_variant 3/3 ENSP00000493234.1 Q15615

Frequencies

GnomAD3 genomes
AF:
0.0000988
AC:
15
AN:
151876
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000113
AC:
25
AN:
220754
Hom.:
0
AF XY:
0.000117
AC XY:
14
AN XY:
119622
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000903
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000561
Gnomad NFE exome
AF:
0.000165
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000684
AC:
98
AN:
1432670
Hom.:
0
Cov.:
32
AF XY:
0.0000844
AC XY:
60
AN XY:
710620
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000496
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000594
Gnomad4 NFE exome
AF:
0.0000746
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.0000988
AC:
15
AN:
151876
Hom.:
0
Cov.:
32
AF XY:
0.0000674
AC XY:
5
AN XY:
74216
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.0000680
ExAC
AF:
0.0000745
AC:
9

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 16, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.25
DANN
Benign
0.68
DEOGEN2
Benign
0.0015
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.34
.;T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.017
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.14
N;N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.34
.;N
REVEL
Benign
0.019
Sift
Benign
0.57
.;T
Sift4G
Benign
0.85
.;T
Polyphen
0.0
B;B
Vest4
0.032
MVP
0.22
MPC
0.085
ClinPred
0.0099
T
GERP RS
-1.5
Varity_R
0.036
gMVP
0.25

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: rs765971383; hg19: chr17-56233440; API