Genetic Variant OR6B3:p.Val312Ile (chr2-240045139-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_173351.2(OR6B3):c.934G>A(p.Val312Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000899 in 1,613,676 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 1 hom. )

Consequence

OR6B3
NM_173351.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.91

Publications

3 publications found

Variant links:

Genes affected

OR6B3 (HGNC:15042): (olfactory receptor family 6 subfamily B 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. [provided by RefSeq, Jul 2008]

OR6B3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032326102).

BP6

Variant 2-240045139-C-T is Benign according to our data. Variant chr2-240045139-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2369001.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173351.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6B3	NM_173351.2	MANE Select	c.934G>A	p.Val312Ile	missense	Exon 3 of 3	NP_775486.1	Q8NGW1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR6B3	ENST00000641019.2	MANE Select	c.934G>A	p.Val312Ile	missense	Exon 3 of 3	ENSP00000493035.1	Q8NGW1
	OR6B3	ENST00000943407.1		c.934G>A	p.Val312Ile	missense	Exon 2 of 2	ENSP00000613466.1

Frequencies

GnomAD3 genomes

AF:

0.000236

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000144

AC:

AN:

249262

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000746

AC:

109

AN:

1461422

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33432

American (AMR)

AF:

0.000560

AC:

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86178

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

1111806

Other (OTH)

AF:

0.000331

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000236

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41470

American (AMR)

AF:

0.00183

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68044

Other (OTH)

AF:

0.00143

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000256

Hom.:

Bravo

AF:

0.000521

ESP6500AA

AF:

0.000270

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.000199

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.011

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.23

M_CAP

Benign

0.0039

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-4.9

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.030

REVEL

Benign

0.023

Sift

Benign

0.38

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.028

MVP

0.14

MPC

0.58

ClinPred

0.027

GERP RS

-3.3

Varity_R

0.019

gMVP

0.063

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over