6-29396866-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013936.4(OR12D2):c.167T>C(p.Leu56Pro) variant causes a missense change. The variant allele was found at a frequency of 0.41 in 1,608,974 control chromosomes in the GnomAD database, including 139,668 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10557 hom., cov: 31)

Exomes 𝑓: 0.42 ( 129111 hom. )

Consequence

OR12D2
NM_013936.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.54

Publications

24 publications found

Variant links:

Genes affected

OR12D2 (HGNC:8178): (olfactory receptor family 12 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. 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]

OR12D2 links:

OR5V1 (HGNC:13972): (olfactory receptor family 5 subfamily V member 1) 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]

OR5V1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018766224).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013936.4. 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
	OR12D2	NM_013936.4	MANE Select	c.167T>C	p.Leu56Pro	missense	Exon 2 of 2	NP_039224.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OR12D2	ENST00000642051.1	MANE Select	c.167T>C	p.Leu56Pro	missense	Exon 2 of 2	ENSP00000493463.1
OR12D2	ENST00000623183.1	TSL:6	c.167T>C	p.Leu56Pro	missense	Exon 1 of 1	ENSP00000485112.1
OR5V1	ENST00000377154.1	TSL:6	c.-83+25741A>G		intron	N/A	ENSP00000366359.1

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54456

AN:

151874

Hom.:

10550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.375

GnomAD2 exomes

AF:

0.391

AC:

96210

AN:

246284

AF XY:

0.389

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.393

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.441

Gnomad OTH exome

AF:

0.407

GnomAD4 exome

AF:

0.416

AC:

605613

AN:

1456982

Hom.:

129111

Cov.:

AF XY:

0.414

AC XY:

299868

AN XY:

725008

show subpopulations

African (AFR)

AF:

0.196

AC:

6559

AN:

33400

American (AMR)

AF:

0.389

AC:

17395

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

12673

AN:

26106

East Asian (EAS)

AF:

0.346

AC:

13730

AN:

39686

South Asian (SAS)

AF:

0.281

AC:

24229

AN:

86168

European-Finnish (FIN)

AF:

0.417

AC:

21814

AN:

52306

Middle Eastern (MID)

AF:

0.360

AC:

2071

AN:

5760

European-Non Finnish (NFE)

AF:

0.436

AC:

482860

AN:

1108570

Other (OTH)

AF:

0.403

AC:

24282

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

18737

37474

56211

74948

93685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14396

28792

43188

57584

71980

<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:

0.358

AC:

54468

AN:

151992

Hom.:

10557

Cov.:

AF XY:

0.359

AC XY:

26637

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.204

AC:

8469

AN:

41478

American (AMR)

AF:

0.371

AC:

5671

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

1720

AN:

3470

East Asian (EAS)

AF:

0.344

AC:

1768

AN:

5146

South Asian (SAS)

AF:

0.264

AC:

1269

AN:

4808

European-Finnish (FIN)

AF:

0.428

AC:

4522

AN:

10564

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.437

AC:

29671

AN:

67928

Other (OTH)

AF:

0.371

AC:

784

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1731

3463

5194

6926

8657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<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:

0.396

Hom.:

18366

Bravo

AF:

0.351

TwinsUK

AF:

0.417

AC:

1545

ALSPAC

AF:

0.442

AC:

1705

ESP6500AA

AF:

0.220

AC:

663

ESP6500EA

AF:

0.444

AC:

2407

ExAC

AF:

0.383

AC:

45073

Asia WGS

AF:

0.255

AC:

889

AN:

3478

EpiCase

AF:

0.432

EpiControl

AF:

0.441

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.036

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.0017

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-3.4

PhyloP100

5.5

PrimateAI

Benign

0.28

Polyphen

0.0

ClinPred

0.0034

GERP RS

3.2

PromoterAI

-0.00090

Neutral

(source)

Varity_R

0.18

gMVP

0.23

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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