chr11-56743286-C-T

Position:

chr11-56743286-C-T

Variant summary

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

The NM_001005284.2(OR9G4):c.481G>A(p.Ala161Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,614,124 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 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

OR9G4
NM_001005284.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.61

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:

OR9G4 (HGNC:):

OR9G4 links:

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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=0.03380677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR9G4	NM_001005284.2 linkuse as main transcript	c.481G>A	p.Ala161Thr	missense_variant	2/2	ENST00000641668.1	NP_001005284.2	Q8NGQ1
OR9G4	NM_001390832.1 linkuse as main transcript	c.481G>A	p.Ala161Thr	missense_variant	2/2		NP_001377761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR9G4	ENST00000641668.1 linkuse as main transcript	c.481G>A	p.Ala161Thr	missense_variant	2/2	NM_001005284.2	ENSP00000493182.1	A0A286YFA5
OR9G4	ENST00000641581.1 linkuse as main transcript	c.481G>A	p.Ala161Thr	missense_variant	2/2		ENSP00000493212.1	A0A286YFA5
OR9G4	ENST00000641505.1 linkuse as main transcript	n.467G>A		non_coding_transcript_exon_variant	2/2
OR9G4	ENST00000641980.1 linkuse as main transcript	n.464G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251480

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000112

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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 submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.526G>A (p.A176T) alteration is located in exon 1 (coding exon 1) of the OR9G4 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the alanine (A) at amino acid position 176 to be replaced by a threonine (T). 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

0.092

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0026

.;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.36

.;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

.;.;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.79

.;.;N

REVEL

Benign

0.059

Sift

Benign

0.61

.;.;T

Sift4G

Benign

0.56

.;.;T

Polyphen

0.026

.;.;B

Vest4

0.092

MVP

0.33

MPC

0.0068

ClinPred

0.044

GERP RS

3.2

Varity_R

0.11

gMVP

0.044

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over