1-158765950-A-G

Variant names:

• chr1-158765950-A-G
• rs857826
• NM_001005185.2:c.733T>C

Variant summary

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

The NM_001005185.2(OR6N1):​c.733T>C​(p.Phe245Leu) 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 1,613,514 control chromosomes in the GnomAD database, including 409,906 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 (39726 hom., cov: 32)
  • Exomes 𝑓: 0.71 (370180 hom.)
• Consequence: OR6N1 NM_001005185.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 31 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=1.1871996E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005185.2. 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
	OR6N1	NM_001005185.2	MANE Select	c.733T>C	p.Phe245Leu	missense	Exon 2 of 2	NP_001005185.1	Q8NGY5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6N1	ENST00000641846.1	MANE Select	c.733T>C	p.Phe245Leu	missense	Exon 2 of 2	ENSP00000493254.1	Q8NGY5
	OR6N1	ENST00000641189.1		n.175+6071T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109532 AN: 152040 Hom.: 39688 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: 0.607

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.687 AC: 172490 AN: 251102 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: 0.690

GnomAD4 exome AF: 0.708 AC: 1034318 AN: 1461356 Hom.: 370180 Cov.: 51 AF XY: 0.699 AC XY: 508061 AN XY: 727002

African (AFR) AF: 0.774 AC: 25928 AN: 33478

American (AMR) AF: 0.788 AC: 35242 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 17138 AN: 26132

East Asian (EAS) AF: 0.619 AC: 24575 AN: 39700

South Asian (SAS) AF: 0.461 AC: 39723 AN: 86244

European-Finnish (FIN) AF: 0.726 AC: 38782 AN: 53418

Middle Eastern (MID) AF: 0.578 AC: 3333 AN: 5766

European-Non Finnish (NFE) AF: 0.726 AC: 807313 AN: 1111524

Other (OTH) AF: 0.700 AC: 42284 AN: 60372

GnomAD4 genome AF: 0.720 AC: 109622 AN: 152158 Hom.: 39726 Cov.: 32 AF XY: 0.713 AC XY: 53036 AN XY: 74400

African (AFR) AF: 0.776 AC: 32181 AN: 41494

American (AMR) AF: 0.756 AC: 11562 AN: 15296

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

East Asian (EAS) AF: 0.607 AC: 3137 AN: 5170

South Asian (SAS) AF: 0.436 AC: 2103 AN: 4824

European-Finnish (FIN) AF: 0.720 AC: 7621 AN: 10588

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

European-Non Finnish (NFE) AF: 0.712 AC: 48430 AN: 68002

Other (OTH) AF: 0.711 AC: 1501 AN: 2110

Alfa AF: 0.705 Hom.: 120895

Bravo AF: 0.732

TwinsUK AF: 0.734 AC: 2721

ALSPAC AF: 0.729 AC: 2810

ESP6500AA AF: 0.780 AC: 3436

ESP6500EA AF: 0.717 AC: 6162

ExAC AF: 0.679 AC: 82485

Asia WGS AF: 0.576 AC: 2006 AN: 3478

EpiCase AF: 0.699

EpiControl AF: 0.696

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.38
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.9	N
PhyloP100		2.9
PrimateAI	Benign	0.30	T
PROVEAN	Benign	3.4	N
REVEL	Benign	0.087
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.071
MutPred		0.32		Gain of glycosylation at T240 (P = 0.1784)
MPC		0.028
ClinPred		0.0035	T
GERP RS		4.7
Varity_R		0.068
gMVP		0.075
Mutation Taster		=95/5	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: rs857826; hg19: chr1-158735740; COSMIC: COSV58647524;