11-5351626-A-G

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.119A>G(p.Asn40Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,613,622 control chromosomes in the GnomAD database, including 32,242 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 0.19 ( 3048 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29194 hom. )

Consequence

OR51B6
NM_001004750.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.21

Publications

23 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=0.001967311).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 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.119A>G	p.Asn40Ser	missense	Exon 1 of 1	NP_001004750.1
OR51B5	NM_001005567.3		c.-359-4716T>C		intron	N/A	NP_001005567.2
OR51B5	NR_038321.2		n.85-4716T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OR51B6	ENST00000380219.1	TSL:6 MANE Select	c.119A>G	p.Asn40Ser	missense	Exon 1 of 1	ENSP00000369568.1
HBE1	ENST00000292896.3	TSL:1	c.-266-81470T>C		intron	N/A	ENSP00000292896.2
HBE1	ENST00000380237.5	TSL:1	c.-309-69675T>C		intron	N/A	ENSP00000369586.1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29513

AN:

151948

Hom.:

3043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.0129

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.185

GnomAD2 exomes

AF:

0.164

AC:

41156

AN:

251282

AF XY:

0.164

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.00941

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.194

AC:

283740

AN:

1461556

Hom.:

29194

Cov.:

AF XY:

0.192

AC XY:

139661

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.211

AC:

7058

AN:

33472

American (AMR)

AF:

0.125

AC:

5567

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

3957

AN:

26134

East Asian (EAS)

AF:

0.00894

AC:

355

AN:

39700

South Asian (SAS)

AF:

0.124

AC:

10711

AN:

86254

European-Finnish (FIN)

AF:

0.194

AC:

10378

AN:

53404

Middle Eastern (MID)

AF:

0.140

AC:

806

AN:

5764

European-Non Finnish (NFE)

AF:

0.210

AC:

233767

AN:

1111738

Other (OTH)

AF:

0.184

AC:

11141

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

12042

24085

36127

48170

60212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7966

15932

23898

31864

39830

<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:

0.194

AC:

29541

AN:

152066

Hom.:

3048

Cov.:

AF XY:

0.191

AC XY:

14210

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.211

AC:

8739

AN:

41466

American (AMR)

AF:

0.167

AC:

2542

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

518

AN:

3470

East Asian (EAS)

AF:

0.0127

AC:

AN:

5180

South Asian (SAS)

AF:

0.122

AC:

589

AN:

4820

European-Finnish (FIN)

AF:

0.194

AC:

2051

AN:

10572

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14414

AN:

67984

Other (OTH)

AF:

0.183

AC:

386

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1223

2446

3669

4892

6115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.198

Hom.:

15666

Bravo

AF:

0.191

TwinsUK

AF:

0.215

AC:

797

ALSPAC

AF:

0.204

AC:

786

ESP6500AA

AF:

0.197

AC:

869

ESP6500EA

AF:

0.212

AC:

1824

ExAC

AF:

0.167

AC:

20224

Asia WGS

AF:

0.112

AC:

388

AN:

3478

EpiCase

AF:

0.202

EpiControl

AF:

0.201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

3.5

PhyloP100

7.2

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.47

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0

Polyphen

0.49

Vest4

0.27

MPC

0.010

ClinPred

0.095

GERP RS

4.0

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.80

gMVP

0.59

Mutation Taster

=51/49

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

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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