17-58170058-G-A

Variant summary

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

The NM_001004707.4(OR4D2):​c.403G>A​(p.Val135Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,000 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

OR4D2
NM_001004707.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200
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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.010225087).
BP6
Variant 17-58170058-G-A is Benign according to our data. Variant chr17-58170058-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2290533.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR4D2NM_001004707.4 linkuse as main transcriptc.403G>A p.Val135Ile missense_variant 2/2 ENST00000545221.2 NP_001004707.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR4D2ENST00000545221.2 linkuse as main transcriptc.403G>A p.Val135Ile missense_variant 2/2 NM_001004707.4 ENSP00000441354 P1
OR4D2ENST00000641866.1 linkuse as main transcriptc.403G>A p.Val135Ile missense_variant 1/1 ENSP00000493137 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152050
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251432
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461832
Hom.:
0
Cov.:
34
AF XY:
0.0000179
AC XY:
13
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000629
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000123
Hom.:
0
Bravo
AF:
0.0000604
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsJun 13, 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
0.075
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
8.6
DANN
Benign
0.60
DEOGEN2
Benign
0.0019
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-0.98
FATHMM_MKL
Benign
0.0073
N
LIST_S2
Benign
0.29
.;T
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.010
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-1.0
N;N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
0.51
N;.
REVEL
Benign
0.021
Sift
Benign
1.0
T;.
Sift4G
Benign
1.0
T;.
Polyphen
0.0
B;B
Vest4
0.061
MVP
0.30
MPC
0.060
ClinPred
0.016
T
GERP RS
0.93
Varity_R
0.038
gMVP
0.13

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: rs200607563; hg19: chr17-56247419; COSMIC: COSV73459699; API