chr6-29396838-G-T

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.139G>T(p.Val47Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,609,628 control chromosomes in the GnomAD database, including 139,694 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 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 ( 10560 hom., cov: 31)

Exomes 𝑓: 0.42 ( 129134 hom. )

Consequence

OR12D2
NM_013936.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.107

Publications

39 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=5.995035E-4).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR12D2	NM_013936.4 link	c.139G>T	p.Val47Phe	missense_variant	Exon 2 of 2	ENST00000642051.1	NP_039224.2	P58182A0A126GV87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR12D2	ENST00000642051.1 link	c.139G>T	p.Val47Phe	missense_variant	Exon 2 of 2		NM_013936.4	ENSP00000493463.1	P58182
OR12D2	ENST00000623183.1 link	c.139G>T	p.Val47Phe	missense_variant	Exon 1 of 1	6		ENSP00000485112.1	P58182
OR5V1	ENST00000377154.1 link	c.-83+25769C>A		intron_variant	Intron 3 of 3	6		ENSP00000366359.1	Q9UGF6

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54465

AN:

151828

Hom.:

10553

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:

0.264

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.375

GnomAD2 exomes

AF:

0.391

AC:

96250

AN:

246362

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:

605985

AN:

1457682

Hom.:

129134

Cov.:

AF XY:

0.414

AC XY:

300030

AN XY:

725308

show subpopulations

African (AFR)

AF:

0.196

AC:

6566

AN:

33416

American (AMR)

AF:

0.389

AC:

17391

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

12677

AN:

26112

East Asian (EAS)

AF:

0.346

AC:

13729

AN:

39684

South Asian (SAS)

AF:

0.281

AC:

24242

AN:

86194

European-Finnish (FIN)

AF:

0.417

AC:

21812

AN:

52306

Middle Eastern (MID)

AF:

0.360

AC:

2075

AN:

5766

European-Non Finnish (NFE)

AF:

0.436

AC:

483212

AN:

1109226

Other (OTH)

AF:

0.403

AC:

24281

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

18840

37681

56521

75362

94202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14416

28832

43248

57664

72080

<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:

0.359

AC:

54477

AN:

151946

Hom.:

10560

Cov.:

AF XY:

0.359

AC XY:

26653

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.205

AC:

8476

AN:

41442

American (AMR)

AF:

0.371

AC:

5678

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

1720

AN:

3470

East Asian (EAS)

AF:

0.344

AC:

1765

AN:

5136

South Asian (SAS)

AF:

0.264

AC:

1273

AN:

4824

European-Finnish (FIN)

AF:

0.429

AC:

4532

AN:

10562

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.437

AC:

29655

AN:

67906

Other (OTH)

AF:

0.371

AC:

784

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1727

3455

5182

6910

8637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.401

Hom.:

29390

Bravo

AF:

0.351

TwinsUK

AF:

0.417

AC:

1545

ALSPAC

AF:

0.442

AC:

1705

ESP6500AA

AF:

0.221

AC:

668

ESP6500EA

AF:

0.445

AC:

2411

ExAC

AF:

0.383

AC:

45029

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.40

.;T

MetaRNN

Benign

0.00060

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;M

PhyloP100

-0.11

PrimateAI

Benign

0.30

Polyphen

0.99

D;D

ClinPred

0.037

GERP RS

3.2

PromoterAI

0.0026

Neutral

(source)

Varity_R

0.35

gMVP

0.46

Mutation Taster

=100/0

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

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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