rs857825

chr1-158765901-T-C

Variant summary

Our verdict is Benign. Variant got -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. 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 0.72 (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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
OR6N1	NM_001005185.2	c.782A>G	p.Gln261Arg	missense_variant	2/2	ENST00000641846.1
OR6N1	XM_017000325.2	c.782A>G	p.Gln261Arg	missense_variant	3/3
OR6N1	XM_017000326.2	c.782A>G	p.Gln261Arg	missense_variant	4/4
OR6N1	XM_017000327.2	c.782A>G	p.Gln261Arg	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR6N1	ENST00000641846.1	c.782A>G	p.Gln261Arg	missense_variant	2/2		NM_001005185.2	P1
OR6N1	ENST00000641189.1	n.175+6120A>G		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.687 AC: 172631 AN: 251342 Hom.: 60650 AF XY: 0.669 AC XY: 90922 AN XY: 135838

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 SAS exome AF: 0.458

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

Gnomad4 AFR exome AF: 0.774

Gnomad4 AMR exome AF: 0.789

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.726

Gnomad4 NFE exome AF: 0.726

Gnomad4 OTH exome AF: 0.700

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

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.710

Alfa AF: 0.706 Hom.: 84811

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
MetaRNN	Benign	0.0000010	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.75	N;N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.34	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

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

Other links and lift over

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