rs12577167

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001004754.3(OR51I2):c.400A>G(p.Thr134Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,613,978 control chromosomes in the GnomAD database, including 18,745 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.13 ( 1598 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17147 hom. )

Consequence

OR51I2
NM_001004754.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

Publications

28 publications found

Variant links:

Genes affected

OR51I2 (HGNC:15201): (olfactory receptor family 51 subfamily I 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]

OR51I2 links:

HBE1 (HGNC:4830): (hemoglobin subunit epsilon 1) The epsilon globin gene (HBE) is normally expressed in the embryonic yolk sac: two epsilon chains together with two zeta chains (an alpha-like globin) constitute the embryonic hemoglobin Hb Gower I; two epsilon chains together with two alpha chains form the embryonic Hb Gower II. Both of these embryonic hemoglobins are normally supplanted by fetal, and later, adult hemoglobin. The five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon - G-gamma - A-gamma - delta - beta-3' [provided by RefSeq, Jul 2008]

HBE1 links:

ENSG00000239920 (HGNC:):

ENSG00000239920 links:

OR51B5 (HGNC:19599): (olfactory receptor family 51 subfamily B member 5) 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]

OR51B5 links:

HBG2 (HGNC:4832): (hemoglobin subunit gamma 2) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'- epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]

HBG2 Gene-Disease associations (from GenCC):

hemoglobinopathy Toms River
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
cyanosis, transient neonatal
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

HBG2 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=0.001234293).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
OR51I2	NM_001004754.3 link	c.400A>G	p.Thr134Ala	missense_variant	Exon 2 of 2	ENST00000641930.1	NP_001004754.1
OR51B5	NM_001005567.3 link	c.-360+51681T>C		intron_variant	Intron 1 of 4		NP_001005567.2
OR51B5	NR_038321.2 link	n.84+51681T>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR51I2	ENST00000641930.1 link	c.400A>G	p.Thr134Ala	missense_variant	Exon 2 of 2		NM_001004754.3	ENSP00000493016.1
ENSG00000239920	ENST00000380259.7 link	n.*740-107989T>C		intron_variant	Intron 5 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20088

AN:

151998

Hom.:

1591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0798

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.151

GnomAD2 exomes

AF:

0.168

AC:

42145

AN:

251436

AF XY:

0.173

show subpopulations

Gnomad AFR exome

AF:

0.0767

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.142

AC:

207852

AN:

1461862

Hom.:

17147

Cov.:

AF XY:

0.147

AC XY:

106567

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0799

AC:

2676

AN:

33480

American (AMR)

AF:

0.176

AC:

7873

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2871

AN:

26136

East Asian (EAS)

AF:

0.339

AC:

13451

AN:

39700

South Asian (SAS)

AF:

0.266

AC:

22974

AN:

86258

European-Finnish (FIN)

AF:

0.118

AC:

6320

AN:

53416

Middle Eastern (MID)

AF:

0.251

AC:

1446

AN:

5768

European-Non Finnish (NFE)

AF:

0.127

AC:

141009

AN:

1111984

Other (OTH)

AF:

0.153

AC:

9232

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

10787

21574

32362

43149

53936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5218

10436

15654

20872

26090

<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:

0.132

AC:

20107

AN:

152116

Hom.:

1598

Cov.:

AF XY:

0.137

AC XY:

10188

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0798

AC:

3311

AN:

41502

American (AMR)

AF:

0.168

AC:

2565

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

377

AN:

3470

East Asian (EAS)

AF:

0.366

AC:

1891

AN:

5160

South Asian (SAS)

AF:

0.282

AC:

1359

AN:

4822

European-Finnish (FIN)

AF:

0.111

AC:

1175

AN:

10590

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.129

AC:

8771

AN:

67978

Other (OTH)

AF:

0.160

AC:

337

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

892

1783

2675

3566

4458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.136

Hom.:

7256

Bravo

AF:

0.131

TwinsUK

AF:

0.127

AC:

472

ALSPAC

AF:

0.138

AC:

531

ESP6500AA

AF:

0.0697

AC:

307

ESP6500EA

AF:

0.127

AC:

1091

ExAC

AF:

0.166

AC:

20194

Asia WGS

AF:

0.292

AC:

1014

AN:

3478

EpiCase

AF:

0.136

EpiControl

AF:

0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.7

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.64

.;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.30

N;N

PhyloP100

-1.4

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-2.5

.;N

REVEL

Benign

0.078

Sift

Benign

0.27

.;T

Sift4G

Benign

0.34

.;T

Polyphen

0.0020

B;B

Vest4

0.017

MPC

0.0084

ClinPred

1.0

GERP RS

1.8

Varity_R

0.076

gMVP

0.13

Mutation Taster

=99/1

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