Variant rs5024042 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001004750.1(OR51B6):c.825C>A(p.Ser275Arg) 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 1,612,696 control chromosomes in the GnomAD database, including 54,612 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 ( 5560 hom., cov: 32)

Exomes 𝑓: 0.26 ( 49052 hom. )

Consequence

OR51B6
NM_001004750.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.132

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=0.005245447).

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	Protein
OR51B6	NM_001004750.1 linkuse as main transcript	c.825C>A	p.Ser275Arg	missense_variant	1/1	ENST00000380219.1	NP_001004750.1
OR51B5	NM_001005567.3 linkuse as main transcript	c.-359-5422G>T		intron_variant			NP_001005567.2
OR51B5	NR_038321.2 linkuse as main transcript	n.85-5422G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR51B6	ENST00000380219.1 linkuse as main transcript	c.825C>A	p.Ser275Arg	missense_variant	1/1		NM_001004750.1	ENSP00000369568	P1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40182

AN:

151960

Hom.:

5550

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:

0.0643

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.236

AC:

59306

AN:

251098

Hom.:

7583

AF XY:

0.235

AC XY:

31882

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.0611

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.255

AC:

372563

AN:

1460616

Hom.:

49052

Cov.:

AF XY:

0.254

AC XY:

184343

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.308

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.0553

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.265

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

AF:

0.264

AC:

40220

AN:

152080

Hom.:

5560

Cov.:

AF XY:

0.262

AC XY:

19473

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.309

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.0638

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.256

Gnomad4 NFE

AF:

0.265

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.257

Hom.:

12741

Bravo

AF:

0.263

TwinsUK

AF:

0.277

AC:

1026

ALSPAC

AF:

0.254

AC:

980

ESP6500AA

AF:

0.292

AC:

1287

ESP6500EA

AF:

0.264

AC:

2270

ExAC

AF:

0.238

AC:

28902

Asia WGS

AF:

0.211

AC:

735

AN:

3476

EpiCase

AF:

0.257

EpiControl

AF:

0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

0.098

Eigen_PC

Benign

-0.073

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

5.7e-9

P;P;P;P

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.17

Sift

Uncertain

0.016

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.61

MutPred

0.29

Gain of methylation at S275 (P = 0.018);

MPC

0.013

ClinPred

0.048

GERP RS

2.3

Varity_R

0.67

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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