Genetic Variant NM_002548.3:c.74G>A (chr17-3092923-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R25W) has been classified as Uncertain significance.

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

Publications

14 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.0672

AC:

16899

AN:

251366

AF XY:

0.0692

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 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

African (AFR)

AF:

0.164

AC:

5483

AN:

33476

American (AMR)

AF:

0.0324

AC:

1451

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0621

AC:

1624

AN:

26134

East Asian (EAS)

AF:

0.00290

AC:

115

AN:

39700

South Asian (SAS)

AF:

0.0910

AC:

7850

AN:

86254

European-Finnish (FIN)

AF:

0.0416

AC:

2220

AN:

53420

Middle Eastern (MID)

AF:

0.0898

AC:

518

AN:

5768

European-Non Finnish (NFE)

AF:

0.0711

AC:

79113

AN:

1111956

Other (OTH)

AF:

0.0730

AC:

4408

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

5395

10789

16184

21578

26973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0870

AC:

13218

AN:

151904

Hom.:

731

Cov.:

AF XY:

0.0843

AC XY:

6258

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.151

AC:

6247

AN:

41366

American (AMR)

AF:

0.0505

AC:

771

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0666

AC:

231

AN:

3468

East Asian (EAS)

AF:

0.00619

AC:

AN:

5166

South Asian (SAS)

AF:

0.0858

AC:

410

AN:

4780

European-Finnish (FIN)

AF:

0.0376

AC:

397

AN:

10568

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0715

AC:

4858

AN:

67970

Other (OTH)

AF:

0.0859

AC:

181

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

595

1190

1785

2380

2975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0805

Hom.:

354

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

(source)

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

PhyloP100

-4.6

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_002548.3:c.74G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over