11-5389801-C-T

Variant names:

Variant summary

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

The NM_001004756.3(OR51M1):c.403C>T(p.Leu135Phe) variant causes a missense change. The variant allele was found at a frequency of 0.798 in 1,613,746 control chromosomes in the GnomAD database, including 517,613 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.78 ( 46249 hom., cov: 32)

Exomes 𝑓: 0.80 ( 471364 hom. )

Consequence

OR51M1
NM_001004756.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.11

Publications

26 publications found

Variant links:

Genes affected

OR51M1 (HGNC:14847): (olfactory receptor family 51 subfamily M member 1) 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]

OR51M1 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=9.523546E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004756.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR51M1	NM_001004756.3	MANE Select	c.403C>T	p.Leu135Phe	missense	Exon 3 of 3	NP_001004756.2	Q9H341
OR51B5	NM_001005567.3		c.-359-42891G>A		intron	N/A	NP_001005567.2	Q9H339
OR51B5	NR_038321.2		n.85-42891G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR51M1	ENST00000642046.1	MANE Select	c.403C>T	p.Leu135Phe	missense	Exon 3 of 3	ENSP00000493005.1	Q9H341
HBE1	ENST00000292896.3	TSL:1	c.-267+115768G>A		intron	N/A	ENSP00000292896.2	P02100
HBE1	ENST00000380237.5	TSL:1	c.-309-107850G>A		intron	N/A	ENSP00000369586.1	P02100

Frequencies

GnomAD3 genomes

AF:

0.776

AC:

117979

AN:

151998

Hom.:

46233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.862

Gnomad AMR

AF:

0.764

Gnomad ASJ

AF:

0.884

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.733

Gnomad FIN

AF:

0.846

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.784

GnomAD2 exomes

AF:

0.768

AC:

191480

AN:

249272

AF XY:

0.775

show subpopulations

Gnomad AFR exome

AF:

0.707

Gnomad AMR exome

AF:

0.683

Gnomad ASJ exome

AF:

0.889

Gnomad EAS exome

AF:

0.510

Gnomad FIN exome

AF:

0.843

Gnomad NFE exome

AF:

0.821

Gnomad OTH exome

AF:

0.796

GnomAD4 exome

AF:

0.801

AC:

1170271

AN:

1461630

Hom.:

471364

Cov.:

AF XY:

0.801

AC XY:

582098

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.716

AC:

23964

AN:

33476

American (AMR)

AF:

0.695

AC:

31084

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.879

AC:

22978

AN:

26136

East Asian (EAS)

AF:

0.516

AC:

20491

AN:

39700

South Asian (SAS)

AF:

0.755

AC:

65159

AN:

86258

European-Finnish (FIN)

AF:

0.838

AC:

44731

AN:

53366

Middle Eastern (MID)

AF:

0.826

AC:

4764

AN:

5768

European-Non Finnish (NFE)

AF:

0.818

AC:

909461

AN:

1111842

Other (OTH)

AF:

0.789

AC:

47639

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

15077

30154

45231

60308

75385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20836

41672

62508

83344

104180

<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:

0.776

AC:

118043

AN:

152116

Hom.:

46249

Cov.:

AF XY:

0.776

AC XY:

57687

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.715

AC:

29639

AN:

41480

American (AMR)

AF:

0.763

AC:

11667

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.884

AC:

3067

AN:

3468

East Asian (EAS)

AF:

0.514

AC:

2658

AN:

5172

South Asian (SAS)

AF:

0.734

AC:

3537

AN:

4820

European-Finnish (FIN)

AF:

0.846

AC:

8968

AN:

10600

Middle Eastern (MID)

AF:

0.833

AC:

245

AN:

294

European-Non Finnish (NFE)

AF:

0.821

AC:

55826

AN:

67972

Other (OTH)

AF:

0.781

AC:

1652

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1317

2635

3952

5270

6587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<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:

0.801

Hom.:

120469

Bravo

AF:

0.763

TwinsUK

AF:

0.818

AC:

3033

ALSPAC

AF:

0.811

AC:

3126

ESP6500AA

AF:

0.738

AC:

3043

ESP6500EA

AF:

0.828

AC:

7025

ExAC

AF:

0.768

AC:

92911

Asia WGS

AF:

0.668

AC:

2322

AN:

3478

EpiCase

AF:

0.828

EpiControl

AF:

0.831

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.00069

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.44

MetaRNN

Benign

9.5e-7

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.8

PhyloP100

5.1

PrimateAI

Benign

0.26

PROVEAN

Benign

5.0

REVEL

Benign

0.097

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.063

MPC

0.011

ClinPred

0.010

GERP RS

5.0

PromoterAI

0.0084

Neutral

(source)

Varity_R

0.045

gMVP

0.050

Mutation Taster

=99/1

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