9-122614808-A-G

Variant names:

• chr9-122614808-A-G
• rs972925
• NM_012364.1:c.71A>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.71A>G​(p.Gln24Arg) variant causes a missense change. The variant allele was found at a frequency of 0.83 in 1,613,582 control chromosomes in the GnomAD database, including 558,812 homozygotes. 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: 𝑓 0.79 (48405 hom., cov: 29)
  • Exomes 𝑓: 0.83 (510407 hom.)
• Consequence: OR1Q1 NM_012364.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87
• Publications: 34 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=1.3050108E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR1Q1	NM_012364.1	c.71A>G	p.Gln24Arg	missense_variant	Exon 1 of 1	ENST00000297913.3	NP_036496.1
LOC124902265	XR_007061759.1	n.344+4758A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1Q1	ENST00000297913.3	c.71A>G	p.Gln24Arg	missense_variant	Exon 1 of 1	6	NM_012364.1	ENSP00000297913.2

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120518 AN: 151856 Hom.: 48381 Cov.: 29

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.785

GnomAD2 exomes AF: 0.845 AC: 212517 AN: 251392 AF XY: 0.848

Gnomad AFR exome AF: 0.664

Gnomad AMR exome AF: 0.890

Gnomad ASJ exome AF: 0.790

Gnomad EAS exome AF: 0.942

Gnomad FIN exome AF: 0.885

Gnomad NFE exome AF: 0.819

Gnomad OTH exome AF: 0.827

GnomAD4 exome AF: 0.834 AC: 1219254 AN: 1461608 Hom.: 510407 Cov.: 51 AF XY: 0.836 AC XY: 607906 AN XY: 727134

African (AFR) AF: 0.658 AC: 22025 AN: 33470

American (AMR) AF: 0.886 AC: 39615 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 20690 AN: 26132

East Asian (EAS) AF: 0.956 AC: 37960 AN: 39700

South Asian (SAS) AF: 0.926 AC: 79849 AN: 86254

European-Finnish (FIN) AF: 0.884 AC: 47212 AN: 53420

Middle Eastern (MID) AF: 0.775 AC: 4471 AN: 5766

European-Non Finnish (NFE) AF: 0.825 AC: 917750 AN: 1111762

Other (OTH) AF: 0.823 AC: 49682 AN: 60386

GnomAD4 genome AF: 0.794 AC: 120593 AN: 151974 Hom.: 48405 Cov.: 29 AF XY: 0.804 AC XY: 59756 AN XY: 74278

African (AFR) AF: 0.670 AC: 27737 AN: 41386

American (AMR) AF: 0.841 AC: 12834 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2735 AN: 3468

East Asian (EAS) AF: 0.944 AC: 4877 AN: 5164

South Asian (SAS) AF: 0.937 AC: 4509 AN: 4814

European-Finnish (FIN) AF: 0.896 AC: 9484 AN: 10584

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55737 AN: 67980

Other (OTH) AF: 0.785 AC: 1654 AN: 2108

Alfa AF: 0.810 Hom.: 234905

Bravo AF: 0.782

TwinsUK AF: 0.831 AC: 3080

ALSPAC AF: 0.827 AC: 3186

ESP6500AA AF: 0.670 AC: 2951

ESP6500EA AF: 0.819 AC: 7047

ExAC AF: 0.839 AC: 101904

Asia WGS AF: 0.893 AC: 3106 AN: 3478

EpiCase AF: 0.807

EpiControl AF: 0.797

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.9
PrimateAI	Benign	0.17	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.092
Sift	Benign	0.070	T
Sift4G	Uncertain	0.027	D
Polyphen		0.0020	B
Vest4		0.053
MPC		0.15
ClinPred		0.015	T
GERP RS		2.9
PromoterAI		0.016	Neutral
Varity_R		0.15
gMVP		0.31
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs972925; hg19: chr9-125377087; COSMIC: COSV52918198; COSMIC: COSV52918198;