1-158766655-C-T

Variant names:

• chr1-158766655-C-T
• rs1864346
• NM_001005185.2:c.28G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001005185.2(OR6N1):​c.28G>A​(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,610,542 control chromosomes in the GnomAD database, including 79,110 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 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 0.25 (5867 hom., cov: 31)
  • Exomes 𝑓: 0.31 (73243 hom.)
• Consequence: OR6N1 NM_001005185.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 30 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6N1	NM_001005185.2	MANE Select	c.28G>A	p.Ala10Thr	missense	Exon 2 of 2	NP_001005185.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6N1	ENST00000641846.1	MANE Select	c.28G>A	p.Ala10Thr	missense	Exon 2 of 2	ENSP00000493254.1
	OR6N1	ENST00000641189.1		n.175+5366G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38046 AN: 152006 Hom.: 5873 Cov.: 31

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.263

GnomAD2 exomes AF: 0.306 AC: 74796 AN: 244698 AF XY: 0.301

Gnomad AFR exome AF: 0.0566

Gnomad AMR exome AF: 0.364

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.421

Gnomad FIN exome AF: 0.378

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.302

GnomAD4 exome AF: 0.312 AC: 454517 AN: 1458418 Hom.: 73243 Cov.: 36 AF XY: 0.308 AC XY: 223760 AN XY: 725560

African (AFR) AF: 0.0506 AC: 1694 AN: 33470

American (AMR) AF: 0.361 AC: 16104 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 8242 AN: 26046

East Asian (EAS) AF: 0.405 AC: 16076 AN: 39680

South Asian (SAS) AF: 0.216 AC: 18605 AN: 86154

European-Finnish (FIN) AF: 0.370 AC: 19344 AN: 52256

Middle Eastern (MID) AF: 0.249 AC: 1432 AN: 5756

European-Non Finnish (NFE) AF: 0.320 AC: 354732 AN: 1110142

Other (OTH) AF: 0.303 AC: 18288 AN: 60318

GnomAD4 genome AF: 0.250 AC: 38028 AN: 152124 Hom.: 5867 Cov.: 31 AF XY: 0.253 AC XY: 18809 AN XY: 74364

African (AFR) AF: 0.0610 AC: 2535 AN: 41542

American (AMR) AF: 0.310 AC: 4731 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3462

East Asian (EAS) AF: 0.412 AC: 2125 AN: 5158

South Asian (SAS) AF: 0.212 AC: 1022 AN: 4826

European-Finnish (FIN) AF: 0.379 AC: 3996 AN: 10546

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21560 AN: 67992

Other (OTH) AF: 0.262 AC: 554 AN: 2116

Alfa AF: 0.292 Hom.: 25927

Bravo AF: 0.242

TwinsUK AF: 0.320 AC: 1185

ALSPAC AF: 0.333 AC: 1285

ESP6500AA AF: 0.0635 AC: 280

ESP6500EA AF: 0.320 AC: 2756

ExAC AF: 0.295 AC: 35751

Asia WGS AF: 0.323 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.23
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.018	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-0.071
PrimateAI	Benign	0.30	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.035
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.013
MPC		0.026
ClinPred		0.00073	T
GERP RS		2.5
Varity_R		0.022
gMVP		0.073
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1864346; hg19: chr1-158736445; COSMIC: COSV58648621;