dbSNP rs1453541: OR4D6:p.Met263Thr (chr11-59457748-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001004708.1(OR4D6):c.788T>C(p.Met263Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,613,562 control chromosomes in the GnomAD database, including 78,107 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.

Frequency

Genomes: 𝑓 0.31 ( 7372 hom., cov: 31)

Exomes 𝑓: 0.31 ( 70735 hom. )

Consequence

OR4D6
NM_001004708.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

Publications

33 publications found

Variant links:

Genes affected

OR4D6 (HGNC:15175): (olfactory receptor family 4 subfamily D member 6) 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]

OR4D6 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=0.0020670593).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4D6	NM_001004708.1 link	c.788T>C	p.Met263Thr	missense_variant	Exon 1 of 1	ENST00000300127.3	NP_001004708.1	Q8NGJ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4D6	ENST00000300127.3 link	c.788T>C	p.Met263Thr	missense_variant	Exon 1 of 1	6	NM_001004708.1	ENSP00000300127.2		Q8NGJ1

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46882

AN:

151916

Hom.:

7358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.288

AC:

72515

AN:

251434

AF XY:

0.287

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.274

Gnomad EAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.323

Gnomad NFE exome

AF:

0.319

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.309

AC:

451146

AN:

1461528

Hom.:

70735

Cov.:

AF XY:

0.306

AC XY:

222638

AN XY:

727064

show subpopulations

African (AFR)

AF:

0.338

AC:

11316

AN:

33478

American (AMR)

AF:

0.252

AC:

11278

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

7429

AN:

26136

East Asian (EAS)

AF:

0.231

AC:

9157

AN:

39696

South Asian (SAS)

AF:

0.231

AC:

19946

AN:

86252

European-Finnish (FIN)

AF:

0.319

AC:

17032

AN:

53416

Middle Eastern (MID)

AF:

0.285

AC:

1641

AN:

5766

European-Non Finnish (NFE)

AF:

0.320

AC:

355452

AN:

1111678

Other (OTH)

AF:

0.296

AC:

17895

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

17031

34061

51092

68122

85153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11588

23176

34764

46352

57940

<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:

0.309

AC:

46950

AN:

152034

Hom.:

7372

Cov.:

AF XY:

0.305

AC XY:

22669

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.338

AC:

14024

AN:

41438

American (AMR)

AF:

0.253

AC:

3861

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

959

AN:

3468

East Asian (EAS)

AF:

0.206

AC:

1064

AN:

5158

South Asian (SAS)

AF:

0.230

AC:

1107

AN:

4814

European-Finnish (FIN)

AF:

0.327

AC:

3461

AN:

10572

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.317

AC:

21552

AN:

67980

Other (OTH)

AF:

0.296

AC:

624

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1634

3269

4903

6538

8172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.310

Hom.:

28652

Bravo

AF:

0.305

TwinsUK

AF:

0.319

AC:

1181

ALSPAC

AF:

0.316

AC:

1218

ESP6500AA

AF:

0.334

AC:

1469

ESP6500EA

AF:

0.316

AC:

2714

ExAC

AF:

0.291

AC:

35348

Asia WGS

AF:

0.262

AC:

907

AN:

3478

EpiCase

AF:

0.323

EpiControl

AF:

0.320

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.89

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0040

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.0018

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.030

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.9

PhyloP100

-1.9

PrimateAI

Benign

0.19

PROVEAN

Benign

3.5

REVEL

Benign

0.030

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.0080

MPC

0.081

ClinPred

0.0031

GERP RS

-2.7

Varity_R

0.034

gMVP

0.34

Mutation Taster

=100/0

polymorphism (auto)

(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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over