9-122615226-A-G

Position:

• chr9-122615226-A-G

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR1Q1	NM_012364.1	c.489A>G	p.Ile163Met	missense_variant	1/1	ENST00000297913.3
LOC124902265	XR_007061759.1	n.344+5176A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR1Q1	ENST00000297913.3	c.489A>G	p.Ile163Met	missense_variant	1/1		NM_012364.1	P1
	ENST00000431442.2	n.4767+5176A>G		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.924 AC: 232301 AN: 251344 Hom.: 107657 AF XY: 0.927 AC XY: 125927 AN XY: 135834

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 SAS exome AF: 0.956

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

Gnomad4 AFR exome AF: 0.744

Gnomad4 AMR exome AF: 0.952

Gnomad4 ASJ exome AF: 0.922

Gnomad4 EAS exome AF: 0.959

Gnomad4 SAS exome AF: 0.955

Gnomad4 FIN exome AF: 0.938

Gnomad4 NFE exome AF: 0.930

Gnomad4 OTH exome AF: 0.919

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

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.960

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.893

Alfa AF: 0.917 Hom.: 114116

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 v4.3

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
MutationTaster	Benign	1.0	P
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
Varity_R		0.041
gMVP		0.065

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

Publications

LitVar

Other links and lift over

dbSNP: rs1329957; hg19: chr9-125377505;