rs857825

Variant names:

• chr1-158765901-T-C
• rs857825
• NM_001005185.2:c.782A>G

Variant summary

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

The NM_001005185.2(OR6N1):​c.782A>G​(p.Gln261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,613,410 control chromosomes in the GnomAD database, including 409,937 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.

• Frequency:
  • Genomes: 𝑓 0.72 (39713 hom., cov: 32)
  • Exomes 𝑓: 0.71 (370224 hom.)
• Consequence: OR6N1 NM_001005185.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 29 publications found

Genes affected

OR6N1 (HGNC:15034): (olfactory receptor family 6 subfamily N 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.037083E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR6N1	NM_001005185.2	c.782A>G	p.Gln261Arg	missense_variant	Exon 2 of 2	ENST00000641846.1	NP_001005185.1
OR6N1	XM_017000325.2	c.782A>G	p.Gln261Arg	missense_variant	Exon 3 of 3		XP_016855814.1
OR6N1	XM_017000326.2	c.782A>G	p.Gln261Arg	missense_variant	Exon 4 of 4		XP_016855815.1
OR6N1	XM_017000327.2	c.782A>G	p.Gln261Arg	missense_variant	Exon 3 of 3		XP_016855816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR6N1	ENST00000641846.1	c.782A>G	p.Gln261Arg	missense_variant	Exon 2 of 2		NM_001005185.2	ENSP00000493254.1
OR6N1	ENST00000641189.1	n.175+6120A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109494 AN: 151994 Hom.: 39675 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.708

GnomAD2 exomes AF: 0.687 AC: 172631 AN: 251342 AF XY: 0.669

Gnomad AFR exome AF: 0.781

Gnomad AMR exome AF: 0.794

Gnomad ASJ exome AF: 0.659

Gnomad EAS exome AF: 0.612

Gnomad FIN exome AF: 0.730

Gnomad NFE exome AF: 0.709

Gnomad OTH exome AF: 0.689

GnomAD4 exome AF: 0.708 AC: 1034325 AN: 1461298 Hom.: 370224 Cov.: 56 AF XY: 0.699 AC XY: 508067 AN XY: 726968

African (AFR) AF: 0.774 AC: 25923 AN: 33478

American (AMR) AF: 0.789 AC: 35266 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 17139 AN: 26134

East Asian (EAS) AF: 0.619 AC: 24563 AN: 39696

South Asian (SAS) AF: 0.460 AC: 39699 AN: 86246

European-Finnish (FIN) AF: 0.726 AC: 38780 AN: 53416

Middle Eastern (MID) AF: 0.578 AC: 3334 AN: 5766

European-Non Finnish (NFE) AF: 0.726 AC: 807343 AN: 1111474

Other (OTH) AF: 0.700 AC: 42278 AN: 60366

GnomAD4 genome AF: 0.720 AC: 109584 AN: 152112 Hom.: 39713 Cov.: 32 AF XY: 0.713 AC XY: 53008 AN XY: 74358

African (AFR) AF: 0.776 AC: 32181 AN: 41482

American (AMR) AF: 0.756 AC: 11551 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2268 AN: 3470

East Asian (EAS) AF: 0.605 AC: 3114 AN: 5144

South Asian (SAS) AF: 0.436 AC: 2102 AN: 4824

European-Finnish (FIN) AF: 0.720 AC: 7616 AN: 10584

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48434 AN: 68016

Other (OTH) AF: 0.710 AC: 1499 AN: 2110

Alfa AF: 0.712 Hom.: 132939

Bravo AF: 0.732

TwinsUK AF: 0.734 AC: 2721

ALSPAC AF: 0.729 AC: 2809

ESP6500AA AF: 0.780 AC: 3436

ESP6500EA AF: 0.717 AC: 6162

ExAC AF: 0.679 AC: 82478

Asia WGS AF: 0.574 AC: 1999 AN: 3478

EpiCase AF: 0.699

EpiControl AF: 0.696

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.16
DEOGEN2	Benign	0.0012	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.032	.;T
MetaRNN	Benign	0.0000010	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.75	N;N
PhyloP100		2.8
PrimateAI	Benign	0.34	T
PROVEAN	Benign	2.6	.;N
REVEL	Benign	0.093
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	.;T
Polyphen		0.0	B;B
Vest4		0.039
MPC		0.027
ClinPred		0.0040	T
GERP RS		4.7
Varity_R		0.034
gMVP		0.069
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs857825; hg19: chr1-158735691; COSMIC: COSV58648258;