NM_001004750.1:c.14A>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.14A>C(p.Lys5Thr) 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 1,610,000 control chromosomes in the GnomAD database, including 54,736 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 ( 5606 hom., cov: 32)

Exomes 𝑓: 0.26 ( 49130 hom. )

Consequence

OR51B6
NM_001004750.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.23

Publications

27 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=0.0020149052).

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.14A>C	p.Lys5Thr	missense	Exon 1 of 1	NP_001004750.1
OR51B5	NM_001005567.3		c.-359-4611T>G		intron	N/A	NP_001005567.2
OR51B5	NR_038321.2		n.85-4611T>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OR51B6	ENST00000380219.1	TSL:6 MANE Select	c.14A>C	p.Lys5Thr	missense	Exon 1 of 1	ENSP00000369568.1
HBE1	ENST00000292896.3	TSL:1	c.-266-81365T>G		intron	N/A	ENSP00000292896.2
HBE1	ENST00000380237.5	TSL:1	c.-309-69570T>G		intron	N/A	ENSP00000369586.1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40282

AN:

151940

Hom.:

5596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.0650

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.261

GnomAD2 exomes

AF:

0.236

AC:

58466

AN:

247736

AF XY:

0.235

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.0610

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.255

AC:

372458

AN:

1457942

Hom.:

49130

Cov.:

AF XY:

0.254

AC XY:

184501

AN XY:

725236

show subpopulations

African (AFR)

AF:

0.310

AC:

10353

AN:

33408

American (AMR)

AF:

0.216

AC:

9596

AN:

44448

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

6464

AN:

25890

East Asian (EAS)

AF:

0.0554

AC:

2197

AN:

39684

South Asian (SAS)

AF:

0.229

AC:

19652

AN:

85676

European-Finnish (FIN)

AF:

0.258

AC:

13702

AN:

53192

Middle Eastern (MID)

AF:

0.193

AC:

1094

AN:

5682

European-Non Finnish (NFE)

AF:

0.265

AC:

294244

AN:

1109742

Other (OTH)

AF:

0.252

AC:

15156

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

13034

26068

39101

52135

65169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9866

19732

29598

39464

49330

<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:

40320

AN:

152058

Hom.:

5606

Cov.:

AF XY:

0.263

AC XY:

19529

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.311

AC:

12882

AN:

41458

American (AMR)

AF:

0.236

AC:

3597

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

882

AN:

3472

East Asian (EAS)

AF:

0.0645

AC:

334

AN:

5176

South Asian (SAS)

AF:

0.230

AC:

1107

AN:

4820

European-Finnish (FIN)

AF:

0.256

AC:

2705

AN:

10574

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

17990

AN:

67972

Other (OTH)

AF:

0.259

AC:

546

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1480

2960

4439

5919

7399

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.:

16944

Bravo

AF:

0.263

TwinsUK

AF:

0.276

AC:

1024

ALSPAC

AF:

0.254

AC:

978

ESP6500AA

AF:

0.295

AC:

1298

ESP6500EA

AF:

0.264

AC:

2268

ExAC

AF:

0.239

AC:

28966

Asia WGS

AF:

0.214

AC:

746

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.042

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.0

PhyloP100

-3.2

PrimateAI

Benign

0.26

PROVEAN

Benign

1.2

REVEL

Benign

0.013

Sift

Benign

0.58

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.060

MPC

0.0033

ClinPred

0.0010

GERP RS

-4.6

PromoterAI

0.028

Neutral

(source)

Varity_R

0.030

gMVP

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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