Variant chr11-124250177-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001002905.2(OR8G1):c.502T>C(p.Phe168Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000403 in 1,613,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

OR8G1
NM_001002905.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37

Variant links:

Genes affected

OR8G1 (HGNC:8484): (olfactory receptor family 8 subfamily G 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. This family member represents a polymorphic pseudogene, whereby some individuals have a functional allele that encodes a full-length protein, while others have a non-functional allele due to the presence of an early stop codon and a 3' end deletion. [provided by RefSeq, Feb 2014]

OR8G1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045663416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8G1	NM_001002905.2 linkuse as main transcript	c.502T>C	p.Phe168Leu	missense_variant	3/3	ENST00000641972.1	NP_001002905.1	Q15617A0A126GVX6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR8G1	ENST00000641972.1 linkuse as main transcript	c.502T>C	p.Phe168Leu	missense_variant	3/3		NM_001002905.2	ENSP00000493289.1		Q15617

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000559

AC:

139

AN:

248800

Hom.:

AF XY:

0.000511

AC XY:

AN XY:

134948

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000465

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.000648

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000407

AC:

595

AN:

1461554

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

274

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00180

Gnomad4 NFE exome

AF:

0.000398

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000368

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000385

Hom.:

Bravo

AF:

0.000348

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.000606

AC:

ExAC

AF:

0.000596

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

Oct 04, 2022

The c.502T>C (p.F168L) alteration is located in exon 1 (coding exon 1) of the OR8G1 gene. This alteration results from a T to C substitution at nucleotide position 502, causing the phenylalanine (F) at amino acid position 168 to be replaced by a leucine (L). 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

Pathogenic

0.83

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.032

T;T

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.046

T;T

PrimateAI

Benign

0.28

Sift4G

Uncertain

0.021

.;D

Polyphen

0.70

P;P

Vest4

0.27

MVP

0.20

GERP RS

2.9

Varity_R

0.090

gMVP

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over