11-5390243-C-A

Position:

chr11-5390243-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004756.3(OR51M1):c.845C>A(p.Pro282His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,614,020 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 51 hom. )

Consequence

OR51M1
NM_001004756.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.25

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:

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005266875).

BS2

High Homozygotes in GnomAdExome4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OR51M1	NM_001004756.3 linkuse as main transcript	c.845C>A	p.Pro282His	missense_variant	3/3	ENST00000642046.1	NP_001004756.2
OR51B5	NM_001005567.3 linkuse as main transcript	c.-359-43333G>T		intron_variant			NP_001005567.2
OR51B5	NR_038321.2 linkuse as main transcript	n.85-43333G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR51M1	ENST00000642046.1 linkuse as main transcript	c.845C>A	p.Pro282His	missense_variant	3/3		NM_001004756.3	ENSP00000493005	P1

Frequencies

GnomAD3 genomes

AF:

0.00474

AC:

722

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00748

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00524

AC:

1306

AN:

249196

Hom.:

AF XY:

0.00523

AC XY:

707

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00894

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00302

Gnomad NFE exome

AF:

0.00925

Gnomad OTH exome

AF:

0.00430

GnomAD4 exome

AF:

0.00671

AC:

9804

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00657

AC XY:

4777

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.00983

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00399

Gnomad4 NFE exome

AF:

0.00794

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.00474

AC:

722

AN:

152324

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00748

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00718

Hom.:

Bravo

AF:

0.00517

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00148

AC:

ESP6500EA

AF:

0.00907

AC:

ExAC

AF:

0.00592

AC:

716

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00583

EpiControl

AF:

0.00830

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.845C>A (p.P282H) alteration is located in exon 1 (coding exon 1) of the OR51M1 gene. This alteration results from a C to A substitution at nucleotide position 845, causing the proline (P) at amino acid position 282 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.3

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0076

T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.14

.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

0.99

D;D;D;N

PrimateAI

Benign

0.17

PROVEAN

Pathogenic

-4.8

.;D

REVEL

Benign

0.069

Sift

Benign

0.25

.;T

Sift4G

Benign

0.26

.;T

Vest4

0.18

MVP

0.29

MPC

0.066

ClinPred

0.073

GERP RS

1.1

Varity_R

0.19

gMVP

0.081

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over