Variant 11-124570489-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001005194.2(OR8A1):c.370G>T(p.Val124Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,613,966 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

OR8A1
NM_001005194.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.659

Variant links:

Genes affected

OR8A1 (HGNC:8469): (olfactory receptor family 8 subfamily A 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. [provided by RefSeq, Jul 2008]

OR8A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27649447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8A1	NM_001005194.2 linkuse as main transcript	c.370G>T	p.Val124Phe	missense_variant	1/1	ENST00000284287.6	NP_001005194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	Appris
OR8A1	ENST00000284287.6 linkuse as main transcript	c.370G>T	p.Val124Phe	missense_variant	1/1	NM_001005194.2	ENSP00000284287	P1
OR8A1	ENST00000642111.1 linkuse as main transcript	c.421G>T	p.Val141Phe	missense_variant	1/1		ENSP00000492999
OR8A1	ENST00000641670.1 linkuse as main transcript	c.370G>T	p.Val124Phe	missense_variant	2/2		ENSP00000492950	P1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000957

AC:

AN:

250746

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000290

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:

0.000186

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000172

AC:

252

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

129

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000112

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.000155

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

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

Aug 21, 2023

The c.421G>T (p.V141F) alteration is located in exon 1 (coding exon 1) of the OR8A1 gene. This alteration results from a G to T substitution at nucleotide position 421, causing the valine (V) at amino acid position 141 to be replaced by a phenylalanine (F). 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

0.25

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.92

.;D;D

M_CAP

Benign

0.0044

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.6

.;M;.

MutationTaster

Benign

0.98

PrimateAI

Benign

0.26

REVEL

Benign

0.19

Polyphen

0.99

.;D;.

MVP

0.54

MPC

0.45

ClinPred

0.92

GERP RS

5.0

Varity_R

0.91

gMVP

0.55

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