9-122615226-A-G

Variant names:

• chr9-122615226-A-G
• rs1329957
• NM_012364.1:c.489A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012364.1(OR1Q1):​c.489A>G​(p.Ile163Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 1,613,942 control chromosomes in the GnomAD database, including 689,731 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I163T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.88 (59459 hom., cov: 30)
  • Exomes 𝑓: 0.93 (630272 hom.)
• Consequence: OR1Q1 NM_012364.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 24 publications found

Genes affected

OR1Q1 (HGNC:8223): (olfactory receptor family 1 subfamily Q member 1) 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]

ENSG00000234156 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.2968224E-7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012364.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1Q1	NM_012364.1	MANE Select	c.489A>G	p.Ile163Met	missense	Exon 1 of 1	NP_036496.1	Q15612

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1Q1	ENST00000297913.3	TSL:6 MANE Select	c.489A>G	p.Ile163Met	missense	Exon 1 of 1	ENSP00000297913.2	Q15612
	ENSG00000234156	ENST00000431442.3	TSL:3	n.4767+5176A>G		intron	N/A
	ENSG00000234156	ENST00000723590.1		n.801+8277A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133856 AN: 152000 Hom.: 59421 Cov.: 30

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.894

GnomAD2 exomes AF: 0.924 AC: 232301 AN: 251344 AF XY: 0.927

Gnomad AFR exome AF: 0.743

Gnomad AMR exome AF: 0.955

Gnomad ASJ exome AF: 0.922

Gnomad EAS exome AF: 0.947

Gnomad FIN exome AF: 0.936

Gnomad NFE exome AF: 0.927

Gnomad OTH exome AF: 0.920

GnomAD4 exome AF: 0.928 AC: 1356584 AN: 1461824 Hom.: 630272 Cov.: 55 AF XY: 0.929 AC XY: 675319 AN XY: 727214

African (AFR) AF: 0.744 AC: 24912 AN: 33478

American (AMR) AF: 0.952 AC: 42580 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 24098 AN: 26136

East Asian (EAS) AF: 0.959 AC: 38086 AN: 39700

South Asian (SAS) AF: 0.955 AC: 82358 AN: 86256

European-Finnish (FIN) AF: 0.938 AC: 50095 AN: 53420

Middle Eastern (MID) AF: 0.910 AC: 5248 AN: 5766

European-Non Finnish (NFE) AF: 0.930 AC: 1033699 AN: 1111954

Other (OTH) AF: 0.919 AC: 55508 AN: 60392

GnomAD4 genome AF: 0.881 AC: 133951 AN: 152118 Hom.: 59459 Cov.: 30 AF XY: 0.887 AC XY: 65940 AN XY: 74364

African (AFR) AF: 0.751 AC: 31115 AN: 41450

American (AMR) AF: 0.929 AC: 14209 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3191 AN: 3470

East Asian (EAS) AF: 0.949 AC: 4897 AN: 5160

South Asian (SAS) AF: 0.960 AC: 4623 AN: 4814

European-Finnish (FIN) AF: 0.943 AC: 10000 AN: 10604

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.925 AC: 62925 AN: 68012

Other (OTH) AF: 0.893 AC: 1885 AN: 2110

Alfa AF: 0.913 Hom.: 235240

Bravo AF: 0.874

TwinsUK AF: 0.934 AC: 3465

ALSPAC AF: 0.935 AC: 3604

ESP6500AA AF: 0.750 AC: 3303

ESP6500EA AF: 0.926 AC: 7966

ExAC AF: 0.920 AC: 111658

Asia WGS AF: 0.926 AC: 3218 AN: 3476

EpiCase AF: 0.923

EpiControl AF: 0.921

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.54
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	9.3e-7	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.25	N
PhyloP100		-0.33
PrimateAI	Benign	0.24	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.14
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.035
MPC		0.14
ClinPred		0.0040	T
GERP RS		5.6
PromoterAI		-0.0046	Neutral
Varity_R		0.041
gMVP		0.065
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1329957; hg19: chr9-125377505; COSMIC: COSV107398920; COSMIC: COSV107398920;