Variant 11-56417683-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001004744.1(OR8U3):c.550T>C(p.Phe184Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,504 control chromosomes in the GnomAD database, including 62,080 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.32 ( 8972 hom., cov: 32)

Exomes 𝑓: 0.26 ( 53108 hom. )

Consequence

OR8U3
NM_001004744.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.141

Variant links:

Genes affected

OR8U3 (HGNC:14841): (olfactory receptor family 8 subfamily U member 3) 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 olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

OR8U3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.1442163E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8U3	NM_001004744.1 linkuse as main transcript	c.550T>C	p.Phe184Leu	missense_variant	1/1	ENST00000623286.1	NP_001004744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR8U3	ENST00000623286.1 linkuse as main transcript	c.550T>C	p.Phe184Leu	missense_variant	1/1		NM_001004744.1	ENSP00000485324	P1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48646

AN:

151884

Hom.:

8962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.306

GnomAD3 exomes

AF:

0.249

AC:

62519

AN:

251032

Hom.:

8784

AF XY:

0.246

AC XY:

33415

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.355

Gnomad EAS exome

AF:

0.117

Gnomad SAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.271

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.263

AC:

384773

AN:

1461502

Hom.:

53108

Cov.:

AF XY:

0.261

AC XY:

189970

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.521

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.353

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.320

AC:

48693

AN:

152002

Hom.:

8972

Cov.:

AF XY:

0.312

AC XY:

23149

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.510

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.134

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.275

Hom.:

12891

Bravo

AF:

0.332

TwinsUK

AF:

0.268

AC:

993

ALSPAC

AF:

0.273

AC:

1051

ESP6500AA

AF:

0.500

AC:

2202

ESP6500EA

AF:

0.279

AC:

2395

ExAC

AF:

0.257

AC:

31191

Asia WGS

AF:

0.169

AC:

592

AN:

3478

EpiCase

AF:

0.266

EpiControl

AF:

0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.32

MetaRNN

Benign

0.000051

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-2.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

Polyphen

0.0

MutPred

0.17

Loss of catalytic residue at C179 (P = 0.1699);

ClinPred

0.0014

GERP RS

2.7

Varity_R

0.092

gMVP

0.031

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