Variant rs10837771 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_033179.2(OR51B4):c.440T>C(p.Met147Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,613,876 control chromosomes in the GnomAD database, including 151,635 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.37 ( 12419 hom., cov: 31)

Exomes 𝑓: 0.43 ( 139216 hom. )

Consequence

OR51B4
NM_033179.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.764

Variant links:

Genes affected

OR51B4 (HGNC:14708): (olfactory receptor family 51 subfamily B member 4) 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]

OR51B4 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:

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:

(HGNC:):

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=2.029782E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR51B4	NM_033179.2 linkuse as main transcript	c.440T>C	p.Met147Thr	missense_variant	1/1	ENST00000380224.2	NP_149419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR51B4	ENST00000380224.2 linkuse as main transcript	c.440T>C	p.Met147Thr	missense_variant	1/1		NM_033179.2	ENSP00000369573	P1

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56977

AN:

151986

Hom.:

12421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.751

Gnomad SAS

AF:

0.538

Gnomad FIN

AF:

0.445

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.437

GnomAD3 exomes

AF:

0.460

AC:

115600

AN:

251410

Hom.:

28544

AF XY:

0.471

AC XY:

63974

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.463

Gnomad ASJ exome

AF:

0.465

Gnomad EAS exome

AF:

0.754

Gnomad SAS exome

AF:

0.542

Gnomad FIN exome

AF:

0.436

Gnomad NFE exome

AF:

0.436

Gnomad OTH exome

AF:

0.474

GnomAD4 exome

AF:

0.429

AC:

627198

AN:

1461774

Hom.:

139216

Cov.:

AF XY:

0.433

AC XY:

314994

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.465

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.713

Gnomad4 SAS exome

AF:

0.537

Gnomad4 FIN exome

AF:

0.436

Gnomad4 NFE exome

AF:

0.415

Gnomad4 OTH exome

AF:

0.444

GnomAD4 genome

AF:

0.375

AC:

56985

AN:

152102

Hom.:

12419

Cov.:

AF XY:

0.382

AC XY:

28425

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.474

Gnomad4 ASJ

AF:

0.452

Gnomad4 EAS

AF:

0.751

Gnomad4 SAS

AF:

0.539

Gnomad4 FIN

AF:

0.445

Gnomad4 NFE

AF:

0.424

Gnomad4 OTH

AF:

0.438

Alfa

AF:

0.422

Hom.:

28266

Bravo

AF:

0.365

TwinsUK

AF:

0.416

AC:

1542

ALSPAC

AF:

0.408

AC:

1571

ESP6500AA

AF:

0.166

AC:

730

ESP6500EA

AF:

0.436

AC:

3745

ExAC

AF:

0.456

AC:

55366

Asia WGS

AF:

0.570

AC:

1983

AN:

3478

EpiCase

AF:

0.445

EpiControl

AF:

0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.4

DANN

Benign

0.55

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.016

MetaRNN

Benign

0.0000020

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.15

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.1

REVEL

Benign

0.016

Sift

Benign

0.26

Sift4G

Benign

0.34

Polyphen

0.016

Vest4

0.022

MPC

0.0082

ClinPred

0.010

GERP RS

2.6

Varity_R

0.11

gMVP

0.11

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

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