11-5389801-C-T

Position:

chr11-5389801-C-T

Variant summary

Our verdict is Benign. Variant got -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. 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 0.78 ( 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

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 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=9.523546E-7).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR51M1	NM_001004756.3 linkuse as main transcript	c.403C>T	p.Leu135Phe	missense_variant	3/3	ENST00000642046.1	NP_001004756.2	Q9H341B2RNI9
OR51B5	NM_001005567.3 linkuse as main transcript	c.-359-42891G>A		intron_variant			NP_001005567.2	Q9H339Q05CQ2
OR51B5	NR_038321.2 linkuse as main transcript	n.85-42891G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR51M1	ENST00000642046.1 linkuse as main transcript	c.403C>T	p.Leu135Phe	missense_variant	3/3		NM_001004756.3	ENSP00000493005.1		Q9H341
ENSG00000239920	ENST00000380259.7 linkuse as main transcript	n.*740-43902G>A		intron_variant		5		ENSP00000369609.3		A0A2U3TZJ3

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

GnomAD3 exomes

AF:

0.768

AC:

191480

AN:

249272

Hom.:

74847

AF XY:

0.775

AC XY:

104800

AN XY:

135234

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 SAS exome

AF:

0.753

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

Gnomad4 AFR exome

AF:

0.716

Gnomad4 AMR exome

AF:

0.695

Gnomad4 ASJ exome

AF:

0.879

Gnomad4 EAS exome

AF:

0.516

Gnomad4 SAS exome

AF:

0.755

Gnomad4 FIN exome

AF:

0.838

Gnomad4 NFE exome

AF:

0.818

Gnomad4 OTH exome

AF:

0.789

GnomAD4 genome

AF:

0.776

AC:

118043

AN:

152116

Hom.:

46249

Cov.:

AF XY:

0.776

AC XY:

57687

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.715

Gnomad4 AMR

AF:

0.763

Gnomad4 ASJ

AF:

0.884

Gnomad4 EAS

AF:

0.514

Gnomad4 SAS

AF:

0.734

Gnomad4 FIN

AF:

0.846

Gnomad4 NFE

AF:

0.821

Gnomad4 OTH

AF:

0.781

Alfa

AF:

0.806

Hom.:

90800

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.00069

T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.44

.;T

MetaRNN

Benign

9.5e-7

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.8

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

5.0

.;N

REVEL

Benign

0.097

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Vest4

0.063

MPC

0.011

ClinPred

0.010

GERP RS

5.0

Varity_R

0.045

gMVP

0.050

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