11-5352081-T-C

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.574T>C(p.Phe192Leu) 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 1,612,566 control chromosomes in the GnomAD database, including 54,851 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.27 ( 5599 hom., cov: 32)

Exomes 𝑓: 0.26 ( 49252 hom. )

Consequence

OR51B6
NM_001004750.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.62

Publications

20 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=0.017346263).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 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.574T>C	p.Phe192Leu	missense	Exon 1 of 1	NP_001004750.1
OR51B5	NM_001005567.3		c.-359-5171A>G		intron	N/A	NP_001005567.2
OR51B5	NR_038321.2		n.85-5171A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OR51B6	ENST00000380219.1	TSL:6 MANE Select	c.574T>C	p.Phe192Leu	missense	Exon 1 of 1	ENSP00000369568.1
HBE1	ENST00000292896.3	TSL:1	c.-266-81925A>G		intron	N/A	ENSP00000292896.2
HBE1	ENST00000380237.5	TSL:1	c.-309-70130A>G		intron	N/A	ENSP00000369586.1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40291

AN:

152028

Hom.:

5589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.0645

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.237

AC:

59658

AN:

251330

AF XY:

0.237

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.0610

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.255

AC:

373129

AN:

1460420

Hom.:

49252

Cov.:

AF XY:

0.254

AC XY:

184826

AN XY:

726626

show subpopulations

African (AFR)

AF:

0.310

AC:

10361

AN:

33444

American (AMR)

AF:

0.219

AC:

9802

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

6550

AN:

26124

East Asian (EAS)

AF:

0.0553

AC:

2193

AN:

39692

South Asian (SAS)

AF:

0.227

AC:

19606

AN:

86234

European-Finnish (FIN)

AF:

0.258

AC:

13765

AN:

53398

Middle Eastern (MID)

AF:

0.193

AC:

1112

AN:

5764

European-Non Finnish (NFE)

AF:

0.265

AC:

294563

AN:

1110730

Other (OTH)

AF:

0.252

AC:

15177

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

17023

34047

51070

68094

85117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9858

19716

29574

39432

49290

<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:

0.265

AC:

40329

AN:

152146

Hom.:

5599

Cov.:

AF XY:

0.263

AC XY:

19533

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.310

AC:

12877

AN:

41488

American (AMR)

AF:

0.236

AC:

3611

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

882

AN:

3472

East Asian (EAS)

AF:

0.0640

AC:

332

AN:

5184

South Asian (SAS)

AF:

0.227

AC:

1093

AN:

4824

European-Finnish (FIN)

AF:

0.256

AC:

2711

AN:

10594

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

17999

AN:

67986

Other (OTH)

AF:

0.260

AC:

549

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1524

3048

4572

6096

7620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<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:

0.246

Hom.:

11995

Bravo

AF:

0.263

TwinsUK

AF:

0.274

AC:

1015

ALSPAC

AF:

0.254

AC:

979

ESP6500AA

AF:

0.221

AC:

973

ESP6500EA

AF:

0.225

AC:

1931

ExAC

AF:

0.239

AC:

29055

Asia WGS

AF:

0.213

AC:

740

AN:

3478

EpiCase

AF:

0.258

EpiControl

AF:

0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Benign

0.15

Eigen_PC

Benign

0.072

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.45

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.5

PhyloP100

-1.6

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.15

Sift

Benign

0.072

Sift4G

Benign

0.27

Polyphen

1.0

Vest4

0.026

MutPred

0.16

Loss of catalytic residue at F192 (P = 0.058)

MPC

0.0040

ClinPred

0.061

GERP RS

5.2

Varity_R

0.32

gMVP

0.11

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

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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