dbSNP rs201592433: OR1L8:p.Arg166Cys (chr9-122567982-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004454.2(OR1L8):c.496C>T(p.Arg166Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000999 in 1,461,858 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 32)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

OR1L8
NM_001004454.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.52

Variant links:

Genes affected

OR1L8 (HGNC:15110): (olfactory receptor family 1 subfamily L member 8) 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]

OR1L8 links:

ENSG00000234156 (HGNC:):

ENSG00000234156 links:

OR1J2 (HGNC:8209): (olfactory receptor family 1 subfamily J member 2) 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]

OR1J2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20200905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR1L8	NM_001004454.2 link	c.496C>T	p.Arg166Cys	missense_variant	Exon 5 of 5	ENST00000641027.1	NP_001004454.1	Q8NGR8A0A126GVC5
OR1L8	XM_017014285.2 link	c.496C>T	p.Arg166Cys	missense_variant	Exon 3 of 4		XP_016869774.1	Q8NGR8A0A126GVC5
OR1L8	XM_017014286.2 link	c.496C>T	p.Arg166Cys	missense_variant	Exon 2 of 2		XP_016869775.1	Q8NGR8A0A126GVC5
OR1J2	XR_007061271.1 link	n.1541-11971G>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1L8	ENST00000641027.1 link	c.496C>T	p.Arg166Cys	missense_variant	Exon 5 of 5		NM_001004454.2	ENSP00000493411.1		Q8NGR8
ENSG00000234156	ENST00000431442.2 link	n.1363-38664G>A		intron_variant	Intron 7 of 9	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

251114

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000999

AC:

146

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000124

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Benign

0.17

PROVEAN

Pathogenic

-5.4

.;D

REVEL

Benign

0.063

Sift

Uncertain

0.0030

.;D

Sift4G

Uncertain

0.0050

.;D

Polyphen

0.17

B;B

Vest4

0.13

MVP

0.37

MPC

0.11

ClinPred

0.29

GERP RS

1.5

Varity_R

0.31

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over