9-122567553-A-C

Position:

chr9-122567553-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004454.2(OR1L8):c.925T>G(p.Ser309Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000707 in 1,570,304 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000042 ( 2 hom. )

Consequence

OR1L8
NM_001004454.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.33

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014218599).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR1L8	NM_001004454.2 linkuse as main transcript	c.925T>G	p.Ser309Ala	missense_variant	5/5	ENST00000641027.1	NP_001004454.1	Q8NGR8A0A126GVC5
OR1L8	XM_017014285.2 linkuse as main transcript	c.925T>G	p.Ser309Ala	missense_variant	3/4		XP_016869774.1	Q8NGR8A0A126GVC5
OR1L8	XM_017014286.2 linkuse as main transcript	c.925T>G	p.Ser309Ala	missense_variant	2/2		XP_016869775.1	Q8NGR8A0A126GVC5
OR1J2	XR_007061271.1 linkuse as main transcript	n.1541-12400A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR1L8	ENST00000641027.1 linkuse as main transcript	c.925T>G	p.Ser309Ala	missense_variant	5/5		NM_001004454.2	ENSP00000493411.1		Q8NGR8
ENSG00000234156	ENST00000431442.2 linkuse as main transcript	n.1363-39093A>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

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:

0.000478

GnomAD3 exomes

AF:

0.0000707

AC:

AN:

212192

Hom.:

AF XY:

0.0000525

AC XY:

AN XY:

114360

show subpopulations

Gnomad AFR exome

AF:

0.000931

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000416

AC:

AN:

1418158

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

702606

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.0000552

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000513

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000274

Gnomad4 OTH exome

AF:

0.000257

GnomAD4 genome

AF:

0.000342

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.000408

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.925T>G (p.S309A) alteration is located in exon 1 (coding exon 1) of the OR1L8 gene. This alteration results from a T to G substitution at nucleotide position 925, causing the serine (S) at amino acid position 309 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.063

DANN

Benign

0.42

DEOGEN2

Benign

0.0041

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.13

.;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.17

.;N

REVEL

Benign

0.038

Sift

Benign

1.0

.;T

Sift4G

Benign

0.39

.;T

Polyphen

0.0

B;B

Vest4

0.097

MVP

0.22

MPC

0.062

ClinPred

0.011

GERP RS

-6.1

Varity_R

0.031

gMVP

0.019

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over