dbSNP rs769423: OR1D2:p.Arg25Gln (chr17-3092923-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002548.3(OR1D2):c.74G>A(p.Arg25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 1,613,724 control chromosomes in the GnomAD database, including 4,762 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.087 ( 731 hom., cov: 31)

Exomes 𝑓: 0.070 ( 4031 hom. )

Consequence

OR1D2
NM_002548.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.56

Variant links:

Genes affected

OR1D2 (HGNC:8183): (olfactory receptor family 1 subfamily D member 2) 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]

OR1D2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015032887).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR1D2	NM_002548.3 link	c.74G>A	p.Arg25Gln	missense_variant	Exon 2 of 2	ENST00000641833.1	NP_002539.2	P34982A0A126GVV4
OR1D2	NM_001386088.1 link	c.74G>A	p.Arg25Gln	missense_variant	Exon 2 of 2		NP_001373017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1D2	ENST00000641833.1 link	c.74G>A	p.Arg25Gln	missense_variant	Exon 2 of 2		NM_002548.3	ENSP00000493103.1		P34982
OR1D2	ENST00000641064.1 link	c.74G>A	p.Arg25Gln	missense_variant	Exon 2 of 2			ENSP00000493077.1		P34982

Frequencies

GnomAD3 genomes

AF:

0.0869

AC:

13197

AN:

151786

Hom.:

729

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.0505

Gnomad ASJ

AF:

0.0666

Gnomad EAS

AF:

0.00618

Gnomad SAS

AF:

0.0855

Gnomad FIN

AF:

0.0376

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0715

Gnomad OTH

AF:

0.0873

GnomAD3 exomes

AF:

0.0672

AC:

16899

AN:

251366

Hom.:

752

AF XY:

0.0692

AC XY:

9403

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.0294

Gnomad ASJ exome

AF:

0.0643

Gnomad EAS exome

AF:

0.00734

Gnomad SAS exome

AF:

0.0891

Gnomad FIN exome

AF:

0.0368

Gnomad NFE exome

AF:

0.0760

Gnomad OTH exome

AF:

0.0634

GnomAD4 exome

AF:

0.0703

AC:

102782

AN:

1461820

Hom.:

4031

Cov.:

AF XY:

0.0712

AC XY:

51814

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.0324

Gnomad4 ASJ exome

AF:

0.0621

Gnomad4 EAS exome

AF:

0.00290

Gnomad4 SAS exome

AF:

0.0910

Gnomad4 FIN exome

AF:

0.0416

Gnomad4 NFE exome

AF:

0.0711

Gnomad4 OTH exome

AF:

0.0730

GnomAD4 genome

AF:

0.0870

AC:

13218

AN:

151904

Hom.:

731

Cov.:

AF XY:

0.0843

AC XY:

6258

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.0505

Gnomad4 ASJ

AF:

0.0666

Gnomad4 EAS

AF:

0.00619

Gnomad4 SAS

AF:

0.0858

Gnomad4 FIN

AF:

0.0376

Gnomad4 NFE

AF:

0.0715

Gnomad4 OTH

AF:

0.0859

Alfa

AF:

0.0807

Hom.:

270

Bravo

AF:

0.0910

TwinsUK

AF:

0.0680

AC:

252

ALSPAC

AF:

0.0623

AC:

240

ESP6500AA

AF:

0.147

AC:

649

ESP6500EA

AF:

0.0697

AC:

599

ExAC

AF:

0.0735

AC:

8919

Asia WGS

AF:

0.0500

AC:

172

AN:

3478

EpiCase

AF:

0.0683

EpiControl

AF:

0.0706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0060

DANN

Benign

0.28

DEOGEN2

Benign

0.0037

T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.0087

.;.;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.83

N;N;N

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.10

.;.;N

REVEL

Benign

0.0070

Sift

Benign

1.0

.;.;T

Sift4G

Benign

0.78

.;.;T

Polyphen

0.0010

B;B;B

Vest4

0.031

MPC

0.088

ClinPred

0.0024

GERP RS

-6.8

Varity_R

0.023

gMVP

0.26

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over