dbSNP rs759952299: OR9G4:p.Arg165Leu (chr11-56743273-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001005284.2(OR9G4):c.494G>T(p.Arg165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

OR9G4
NM_001005284.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.05

Variant links:

Genes affected

OR9G4 (HGNC:15322): (olfactory receptor family 9 subfamily G member 4) 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]

OR9G4 links:

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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=0.19267985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR9G4	NM_001005284.2 link	c.494G>T	p.Arg165Leu	missense_variant	Exon 2 of 2	ENST00000641668.1	NP_001005284.2	Q8NGQ1
OR9G4	NM_001390832.1 link	c.494G>T	p.Arg165Leu	missense_variant	Exon 2 of 2		NP_001377761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR9G4	ENST00000641668.1 link	c.494G>T	p.Arg165Leu	missense_variant	Exon 2 of 2	NM_001005284.2	ENSP00000493182.1	A0A286YFA5
OR9G4	ENST00000641581.1 link	c.494G>T	p.Arg165Leu	missense_variant	Exon 2 of 2		ENSP00000493212.1	A0A286YFA5
OR9G4	ENST00000641505.1 link	n.480G>T		non_coding_transcript_exon_variant	Exon 2 of 2
OR9G4	ENST00000641980.1 link	n.477G>T		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251464

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

.;.;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.60

.;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

.;.;L

PrimateAI

Benign

0.18

PROVEAN

Uncertain

-3.5

.;.;D

REVEL

Benign

0.072

Sift

Benign

0.037

.;.;D

Sift4G

Uncertain

0.054

.;.;T

Polyphen

0.85

.;.;P

Vest4

0.48

MVP

0.38

MPC

0.012

ClinPred

0.66

GERP RS

0.88

Varity_R

0.21

gMVP

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over