11-56743496-G-A

Position:

chr11-56743496-G-A

Variant summary

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

The NM_001005284.2(OR9G4):c.271C>T(p.Arg91Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,614,090 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

OR9G4
NM_001005284.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.881

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:

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=0.029834569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR9G4	NM_001005284.2 linkuse as main transcript	c.271C>T	p.Arg91Cys	missense_variant	2/2	ENST00000641668.1	NP_001005284.2	Q8NGQ1
OR9G4	NM_001390832.1 linkuse as main transcript	c.271C>T	p.Arg91Cys	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.271C>T	p.Arg91Cys	missense_variant	2/2	NM_001005284.2	ENSP00000493182.1	A0A286YFA5
OR9G4	ENST00000641581.1 linkuse as main transcript	c.271C>T	p.Arg91Cys	missense_variant	2/2		ENSP00000493212.1	A0A286YFA5
OR9G4	ENST00000641505.1 linkuse as main transcript	n.257C>T		non_coding_transcript_exon_variant	2/2
OR9G4	ENST00000641980.1 linkuse as main transcript	n.254C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251458

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000376

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Sep 17, 2021

The c.316C>T (p.R106C) alteration is located in exon 1 (coding exon 1) of the OR9G4 gene. This alteration results from a C to T substitution at nucleotide position 316, causing the arginine (R) at amino acid position 106 to be replaced by a cysteine (C). 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

0.14

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0061

.;.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.72

.;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.030

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.3

.;.;L

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.44

.;.;N

REVEL

Benign

0.091

Sift

Benign

0.079

.;.;T

Sift4G

Uncertain

0.040

.;.;D

Polyphen

0.032

.;.;B

Vest4

0.14

MVP

0.15

MPC

0.014

ClinPred

0.091

GERP RS

2.1

Varity_R

0.11

gMVP

0.096

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