dbSNP rs10985760: OR1L6:p.Ile215Asn (chr9-122750491-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001004453.3(OR1L6):c.644T>A(p.Ile215Asn) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 16)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR1L6
NM_001004453.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.83

Publications

18 publications found

Variant links:

Genes affected

OR1L6 (HGNC:8218): (olfactory receptor family 1 subfamily L member 6) 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]

OR1L6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.784

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004453.3. 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
	OR1L6	NM_001004453.3	MANE Select	c.644T>A	p.Ile215Asn	missense	Exon 2 of 2	NP_001004453.2	A0A0C4DFP2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1L6	ENST00000304720.3	TSL:6 MANE Select	c.644T>A	p.Ile215Asn	missense	Exon 2 of 2	ENSP00000304235.2	A0A0C4DFP2
	OR1L6	ENST00000373684.1	TSL:6	c.752T>A	p.Ile251Asn	missense	Exon 1 of 1	ENSP00000362788.1	Q8NGR2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

132690

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000350

AC:

AN:

856484

Hom.:

Cov.:

AF XY:

0.00000450

AC XY:

AN XY:

444358

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

24448

American (AMR)

AF:

0.00

AC:

AN:

41484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20034

East Asian (EAS)

AF:

0.00

AC:

AN:

36676

South Asian (SAS)

AF:

0.00

AC:

AN:

67978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3198

European-Non Finnish (NFE)

AF:

0.00000349

AC:

AN:

572640

Other (OTH)

AF:

0.0000247

AC:

AN:

40478

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0160444), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

132690

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

63178

African (AFR)

AF:

0.00

AC:

AN:

36032

American (AMR)

AF:

0.00

AC:

AN:

12504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3208

East Asian (EAS)

AF:

0.00

AC:

AN:

4432

South Asian (SAS)

AF:

0.00

AC:

AN:

3444

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

61542

Other (OTH)

AF:

0.00

AC:

AN:

1696

Alfa

AF:

0.00

Hom.:

17110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.78

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.0030

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

PhyloP100

4.8

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Varity_R

0.77

gMVP

0.41

Mutation Taster

=100/0

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over