rs5006884

chr11-5352021-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001004750.1(OR51B6):c.514C>T(p.Leu172Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,603,842 control chromosomes in the GnomAD database, including 54,593 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.26 ( 5515 hom., cov: 32)

Exomes 𝑓: 0.25 ( 49078 hom. )

Consequence

OR51B6
NM_001004750.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.668

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:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068277717).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR51B6	NM_001004750.1 linkuse as main transcript	c.514C>T	p.Leu172Phe	missense_variant	1/1	ENST00000380219.1
OR51B5	NM_001005567.3 linkuse as main transcript	c.-359-5111G>A		intron_variant
OR51B5	NR_038321.2 linkuse as main transcript	n.85-5111G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR51B6	ENST00000380219.1 linkuse as main transcript	c.514C>T	p.Leu172Phe	missense_variant	1/1		NM_001004750.1	P1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40104

AN:

151854

Hom.:

5505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.0646

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.237

AC:

59344

AN:

250830

Hom.:

7604

AF XY:

0.236

AC XY:

31951

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.216

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.0611

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.254

AC:

368522

AN:

1451870

Hom.:

49078

Cov.:

AF XY:

0.253

AC XY:

182702

AN XY:

722682

show subpopulations

Gnomad4 AFR exome

AF:

0.307

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.0551

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.264

AC:

40142

AN:

151972

Hom.:

5515

Cov.:

AF XY:

0.261

AC XY:

19420

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.308

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.0641

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.256

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.257

Hom.:

11775

Bravo

AF:

0.263

TwinsUK

AF:

0.274

AC:

1017

ALSPAC

AF:

0.251

AC:

966

ESP6500AA

AF:

0.292

AC:

1285

ESP6500EA

AF:

0.264

AC:

2270

ExAC

AF:

0.239

AC:

28970

Asia WGS

AF:

0.212

AC:

739

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

0.14

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

0.13

Eigen_PC

Benign

-0.080

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

0.000026

P;P;P;P

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.092

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.14

MPC

0.013

ClinPred

0.049

GERP RS

3.3

Varity_R

0.79

gMVP

0.029

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over