Variant 11-124250271-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.596T>C(p.Ile199Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,613,774 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

OR8G1
NM_001002905.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.748

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=0.023183137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8G1	NM_001002905.2 link	c.596T>C	p.Ile199Thr	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 link	c.596T>C	p.Ile199Thr	missense_variant	3/3		NM_001002905.2	ENSP00000493289.1		Q15617

Frequencies

GnomAD3 genomes

AF:

0.000920

AC:

140

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000739

AC:

184

AN:

248966

Hom.:

AF XY:

0.000778

AC XY:

105

AN XY:

135040

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.00105

AC:

1530

AN:

1461520

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

756

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00137

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.000961

GnomAD4 genome

AF:

0.000920

AC:

140

AN:

152254

Hom.:

Cov.:

AF XY:

0.000927

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000907

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000758

AC:

ESP6500EA

AF:

0.00132

AC:

ExAC

AF:

0.000777

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

Dec 07, 2021

The c.596T>C (p.I199T) 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 596, causing the isoleucine (I) at amino acid position 199 to be replaced by a threonine (T). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.026

T;T

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.16

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.023

T;T

PrimateAI

Benign

0.25

Sift4G

Uncertain

0.060

.;T

Polyphen

0.43

B;B

Vest4

0.18

MVP

0.34

GERP RS

1.7

Varity_R

0.060

gMVP

0.076

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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