rs5024042

Variant names:

Variant summary

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

The NM_001004750.1(OR51B6):c.825C>A(p.Ser275Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,612,696 control chromosomes in the GnomAD database, including 54,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5560 hom., cov: 32)

Exomes 𝑓: 0.26 ( 49052 hom. )

Consequence

OR51B6
NM_001004750.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.132

Publications

28 publications found

Variant links:

Genes affected

OR51B6 (HGNC:19600): (olfactory receptor family 51 subfamily B 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]

OR51B6 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=0.005245447).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004750.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OR51B6	NM_001004750.1	MANE Select	c.825C>A	p.Ser275Arg	missense	Exon 1 of 1	NP_001004750.1
OR51B5	NM_001005567.3		c.-359-5422G>T		intron	N/A	NP_001005567.2
OR51B5	NR_038321.2		n.85-5422G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OR51B6	ENST00000380219.1	TSL:6 MANE Select	c.825C>A	p.Ser275Arg	missense	Exon 1 of 1	ENSP00000369568.1
HBE1	ENST00000292896.3	TSL:1	c.-266-82176G>T		intron	N/A	ENSP00000292896.2
HBE1	ENST00000380237.5	TSL:1	c.-309-70381G>T		intron	N/A	ENSP00000369586.1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40182

AN:

151960

Hom.:

5550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.0643

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.261

GnomAD2 exomes

AF:

0.236

AC:

59306

AN:

251098

AF XY:

0.235

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.0611

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.255

AC:

372563

AN:

1460616

Hom.:

49052

Cov.:

AF XY:

0.254

AC XY:

184343

AN XY:

726630

show subpopulations

African (AFR)

AF:

0.308

AC:

10290

AN:

33450

American (AMR)

AF:

0.219

AC:

9795

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

6547

AN:

26114

East Asian (EAS)

AF:

0.0553

AC:

2193

AN:

39692

South Asian (SAS)

AF:

0.220

AC:

18965

AN:

86234

European-Finnish (FIN)

AF:

0.258

AC:

13759

AN:

53390

Middle Eastern (MID)

AF:

0.193

AC:

1110

AN:

5760

European-Non Finnish (NFE)

AF:

0.265

AC:

294755

AN:

1110922

Other (OTH)

AF:

0.251

AC:

15149

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

13715

27431

41146

54862

68577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9864

19728

29592

39456

49320

<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:

0.264

AC:

40220

AN:

152080

Hom.:

5560

Cov.:

AF XY:

0.262

AC XY:

19473

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.309

AC:

12803

AN:

41468

American (AMR)

AF:

0.236

AC:

3617

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

881

AN:

3472

East Asian (EAS)

AF:

0.0638

AC:

330

AN:

5170

South Asian (SAS)

AF:

0.220

AC:

1059

AN:

4822

European-Finnish (FIN)

AF:

0.256

AC:

2705

AN:

10546

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

18003

AN:

67990

Other (OTH)

AF:

0.259

AC:

546

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1501

3002

4503

6004

7505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.259

Hom.:

18028

Bravo

AF:

0.263

TwinsUK

AF:

0.277

AC:

1026

ALSPAC

AF:

0.254

AC:

980

ESP6500AA

AF:

0.292

AC:

1287

ESP6500EA

AF:

0.264

AC:

2270

ExAC

AF:

0.238

AC:

28902

Asia WGS

AF:

0.211

AC:

735

AN:

3476

EpiCase

AF:

0.257

EpiControl

AF:

0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

0.098

Eigen_PC

Benign

-0.073

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

3.5

PhyloP100

0.13

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.17

Sift

Uncertain

0.016

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.61

MutPred

0.29

Gain of methylation at S275 (P = 0.018)

MPC

0.013

ClinPred

0.048

GERP RS

2.3

Varity_R

0.67

gMVP

0.44

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over