17-58169708-C-T

Variant summary

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

The NM_001004707.4(OR4D2):​c.53C>T​(p.Ser18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

OR4D2
NM_001004707.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00
Variant links:
Genes affected
OR4D2 (HGNC:8294): (olfactory receptor family 4 subfamily D member 2) 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=0.052890003).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR4D2NM_001004707.4 linkc.53C>T p.Ser18Leu missense_variant Exon 2 of 2 ENST00000545221.2 NP_001004707.1 P58180A0A126GWK0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR4D2ENST00000545221.2 linkc.53C>T p.Ser18Leu missense_variant Exon 2 of 2 6 NM_001004707.4 ENSP00000441354.1 P58180
OR4D2ENST00000641866.1 linkc.53C>T p.Ser18Leu missense_variant Exon 1 of 1 ENSP00000493137.1 P58180

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152140
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000771
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251488
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000326
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:
0.00000821
AC:
12
AN:
1461846
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152258
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000772
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 28, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.53C>T (p.S18L) alteration is located in exon 1 (coding exon 1) of the OR4D2 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the serine (S) at amino acid position 18 to be replaced by a leucine (L). 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
0.19
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.017
T;T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.53
D
LIST_S2
Uncertain
0.89
.;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.053
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-3.5
D;.
REVEL
Benign
0.12
Sift
Uncertain
0.0090
D;.
Sift4G
Uncertain
0.012
D;.
Polyphen
0.0080
B;B
Vest4
0.40
MutPred
0.52
Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP
0.35
MPC
0.069
ClinPred
0.19
T
GERP RS
4.4
Varity_R
0.15
gMVP
0.11

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: rs568882234; hg19: chr17-56247069; API