Variant chr11-56417871-T-C 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.362A>G(p.Asp121Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 1,613,608 control chromosomes in the GnomAD database, including 5,011 homozygotes. In-silico tool predicts 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D121N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.058 ( 379 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4632 hom. )

Consequence

OR8U3
NM_001004744.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.95

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=0.0032057762).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR8U3	NM_001004744.1 linkuse as main transcript	c.362A>G	p.Asp121Gly	missense_variant	1/1	ENST00000623286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR8U3	ENST00000623286.1 linkuse as main transcript	c.362A>G	p.Asp121Gly	missense_variant	1/1		NM_001004744.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0579

AC:

8807

AN:

152024

Hom.:

379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0468

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0569

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0834

Gnomad OTH

AF:

0.0646

GnomAD3 exomes

AF:

0.0643

AC:

16135

AN:

251040

Hom.:

711

AF XY:

0.0660

AC XY:

8953

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.0323

Gnomad ASJ exome

AF:

0.0252

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0512

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.0857

Gnomad OTH exome

AF:

0.0747

GnomAD4 exome

AF:

0.0750

AC:

109633

AN:

1461466

Hom.:

4632

Cov.:

AF XY:

0.0747

AC XY:

54283

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.0337

Gnomad4 ASJ exome

AF:

0.0252

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0516

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.0816

Gnomad4 OTH exome

AF:

0.0717

GnomAD4 genome

AF:

0.0579

AC:

8803

AN:

152142

Hom.:

379

Cov.:

AF XY:

0.0584

AC XY:

4342

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0128

Gnomad4 AMR

AF:

0.0467

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.0572

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.0833

Gnomad4 OTH

AF:

0.0639

Alfa

AF:

0.0739

Hom.:

887

Bravo

AF:

0.0493

TwinsUK

AF:

0.0744

AC:

276

ALSPAC

AF:

0.0812

AC:

313

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.0808

AC:

694

ExAC

AF:

0.0654

AC:

7944

Asia WGS

AF:

0.0300

AC:

106

AN:

3478

EpiCase

AF:

0.0816

EpiControl

AF:

0.0796

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

Polyphen

1.0

ClinPred

0.079

GERP RS

5.8

Varity_R

0.65

gMVP

0.37

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