Genetic Variant OR6N1:p.Ala10Thr (chr1-158766655-C-T) – ACMG Classification: Benign (-8 pts)

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0710

Publications

30 publications found

Variant links:

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]

OR6N1 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR6N1	NM_001005185.2 link	c.28G>A	p.Ala10Thr	missense_variant	Exon 2 of 2	ENST00000641846.1	NP_001005185.1	Q8NGY5
OR6N1	XM_017000325.2 link	c.28G>A	p.Ala10Thr	missense_variant	Exon 3 of 3		XP_016855814.1	Q8NGY5
OR6N1	XM_017000326.2 link	c.28G>A	p.Ala10Thr	missense_variant	Exon 4 of 4		XP_016855815.1	Q8NGY5
OR6N1	XM_017000327.2 link	c.28G>A	p.Ala10Thr	missense_variant	Exon 3 of 3		XP_016855816.1	Q8NGY5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR6N1	ENST00000641846.1 link	c.28G>A	p.Ala10Thr	missense_variant	Exon 2 of 2		NM_001005185.2	ENSP00000493254.1		Q8NGY5
OR6N1	ENST00000641189.1 link	n.175+5366G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38046

AN:

152006

Hom.:

5873

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.308

AC XY:

223760

AN XY:

725560

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

14546

29092

43638

58184

72730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.250

AC:

38028

AN:

152124

Hom.:

5867

Cov.:

AF XY:

0.253

AC XY:

18809

AN XY:

74364

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.317

AC:

21560

AN:

67992

Other (OTH)

AF:

0.262

AC:

554

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1363

2726

4088

5451

6814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.4

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.0019

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.018

.;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.6

N;N

PhyloP100

-0.071

PrimateAI

Benign

0.30

PROVEAN

Benign

2.2

.;N

REVEL

Benign

0.035

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0

B;B

Vest4

0.013

MPC

0.026

ClinPred

0.00073

GERP RS

2.5

Varity_R

0.022

gMVP

0.073

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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1-158766655-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over