11-5351776-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.269T>C(p.Ile90Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,613,078 control chromosomes in the GnomAD database, including 54,877 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 0.27 ( 5607 hom., cov: 32)

Exomes 𝑓: 0.26 ( 49270 hom. )

Consequence

OR51B6
NM_001004750.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

Publications

25 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=0.0016942918).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51B6	NM_001004750.1 link	c.269T>C	p.Ile90Thr	missense_variant	Exon 1 of 1	ENST00000380219.1	NP_001004750.1	Q9H340
OR51B5	NM_001005567.3 link	c.-359-4866A>G		intron_variant	Intron 1 of 4		NP_001005567.2	Q9H339Q05CQ2
OR51B5	NR_038321.2 link	n.85-4866A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR51B6	ENST00000380219.1 link	c.269T>C	p.Ile90Thr	missense_variant	Exon 1 of 1	6	NM_001004750.1	ENSP00000369568.1		Q9H340
ENSG00000239920	ENST00000380259.7 link	n.*740-5877A>G		intron_variant	Intron 5 of 7	5		ENSP00000369609.3		A0A2U3TZJ3

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40292

AN:

151962

Hom.:

5597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.0649

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:

59587

AN:

250990

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:

0.0611

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.256

AC:

373429

AN:

1460998

Hom.:

49270

Cov.:

AF XY:

0.254

AC XY:

184943

AN XY:

726856

show subpopulations

African (AFR)

AF:

0.310

AC:

10374

AN:

33466

American (AMR)

AF:

0.219

AC:

9809

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

6548

AN:

26120

East Asian (EAS)

AF:

0.0553

AC:

2196

AN:

39696

South Asian (SAS)

AF:

0.227

AC:

19608

AN:

86216

European-Finnish (FIN)

AF:

0.258

AC:

13749

AN:

53374

Middle Eastern (MID)

AF:

0.193

AC:

1114

AN:

5766

European-Non Finnish (NFE)

AF:

0.265

AC:

294844

AN:

1111290

Other (OTH)

AF:

0.252

AC:

15187

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

15340

30679

46019

61358

76698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9868

19736

29604

39472

49340

<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:

40330

AN:

152080

Hom.:

5607

Cov.:

AF XY:

0.263

AC XY:

19544

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.311

AC:

12886

AN:

41490

American (AMR)

AF:

0.236

AC:

3611

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

881

AN:

3470

East Asian (EAS)

AF:

0.0644

AC:

334

AN:

5184

South Asian (SAS)

AF:

0.227

AC:

1094

AN:

4816

European-Finnish (FIN)

AF:

0.256

AC:

2712

AN:

10576

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

17986

AN:

67954

Other (OTH)

AF:

0.260

AC:

549

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1484

2967

4451

5934

7418

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:

0.256

Hom.:

17401

Bravo

AF:

0.263

TwinsUK

AF:

0.276

AC:

1025

ALSPAC

AF:

0.255

AC:

981

ESP6500AA

AF:

0.295

AC:

1298

ESP6500EA

AF:

0.264

AC:

2268

ExAC

AF:

0.239

AC:

29064

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.4

PhyloP100

1.1

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.21

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.020

Polyphen

0.45

Vest4

0.24

MPC

0.0043

ClinPred

0.096

GERP RS

5.0

PromoterAI

0.017

Neutral

(source)

Varity_R

0.54

gMVP

0.054

Mutation Taster

=66/34

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over