rs12577167

Variant summary

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

The NM_001004754.3(OR51I2):c.400A>G(p.Thr134Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,613,978 control chromosomes in the GnomAD database, including 18,745 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.13 ( 1598 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17147 hom. )

Consequence

OR51I2
NM_001004754.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

Variant links:

Genes affected

OR51I2 (HGNC:15201): (olfactory receptor family 51 subfamily I member 2) 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]

OR51I2 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=0.001234293).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR51I2	NM_001004754.3 linkuse as main transcript	c.400A>G	p.Thr134Ala	missense_variant	2/2	ENST00000641930.1
OR51B5	NM_001005567.3 linkuse as main transcript	c.-360+51681T>C		intron_variant
OR51B5	NR_038321.2 linkuse as main transcript	n.84+51681T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR51I2	ENST00000641930.1 linkuse as main transcript	c.400A>G	p.Thr134Ala	missense_variant	2/2		NM_001004754.3	P1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20088

AN:

151998

Hom.:

1591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0798

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.168

AC:

42145

AN:

251436

Hom.:

4426

AF XY:

0.173

AC XY:

23502

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0767

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.371

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.142

AC:

207852

AN:

1461862

Hom.:

17147

Cov.:

AF XY:

0.147

AC XY:

106567

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0799

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.339

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.132

AC:

20107

AN:

152116

Hom.:

1598

Cov.:

AF XY:

0.137

AC XY:

10188

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0798

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.138

Hom.:

4046

Bravo

AF:

0.131

TwinsUK

AF:

0.127

AC:

472

ALSPAC

AF:

0.138

AC:

531

ESP6500AA

AF:

0.0697

AC:

307

ESP6500EA

AF:

0.127

AC:

1091

ExAC

AF:

0.166

AC:

20194

Asia WGS

AF:

0.292

AC:

1014

AN:

3478

EpiCase

AF:

0.136

EpiControl

AF:

0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

Cadd

Benign

8.7

Dann

Benign

0.95

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.12

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.30

N;N

MutationTaster

Benign

0.016

P;P;P;P

PrimateAI

Benign

0.22

Polyphen

0.0020

B;B

Vest4

0.017

MPC

0.0084

ClinPred

1.0

GERP RS

1.8

Varity_R

0.076

gMVP

0.13

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