Genetic Variant OR4M2:p.Arg150Ser (chr15-22081074-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004719.2(OR4M2):c.450G>C(p.Arg150Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 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 the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR4M2
NM_001004719.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.96

Publications

3 publications found

Variant links:

Genes affected

OR4M2 (HGNC:15373): (olfactory receptor family 4 subfamily M 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]

OR4M2 links:

OR4M2-OT1 (HGNC:56199): (OR4M2 overlapping transcript 1)

OR4M2-OT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037472486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4M2	NM_001004719.2 link	c.450G>C	p.Arg150Ser	missense_variant	Exon 1 of 1	ENST00000614722.3	NP_001004719.2	Q8NGB6
OR4M2-OT1	NR_110480.2 link	n.824-13439G>C		intron_variant	Intron 7 of 8
OR4M2-OT1	NR_110481.2 link	n.556-13439G>C		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR4M2	ENST00000614722.3 link	c.450G>C	p.Arg150Ser	missense_variant	Exon 1 of 1	6	NM_001004719.2	ENSP00000483239.1	Q8NGB6
OR4M2-OT1	ENST00000639059.1 link	c.-9-13439G>C		intron_variant	Intron 6 of 6	2		ENSP00000493899.1
OR4M2	ENST00000638815.1 link	n.485G>C		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

1844

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251412

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

80802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

43548

African (AFR)

AF:

0.00

AC:

AN:

6112

American (AMR)

AF:

0.00

AC:

AN:

3146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2404

East Asian (EAS)

AF:

0.00

AC:

AN:

2482

South Asian (SAS)

AF:

0.00

AC:

AN:

12818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

530

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

43968

Other (OTH)

AF:

0.00

AC:

AN:

5232

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1860

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

854

African (AFR)

AF:

0.00

AC:

AN:

1260

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

350

Other (OTH)

AF:

0.00

AC:

AN:

Alfa

AF:

0.000118

Hom.:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.53

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.23

M_CAP

Benign

0.0024

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.9

PhyloP100

-4.0

Sift4G

Uncertain

0.053

Polyphen

0.0

Vest4

0.040

MutPred

0.39

Gain of glycosylation at R150 (P = 0.0166);

MVP

0.19

ClinPred

0.037

GERP RS

1.1

Varity_R

0.10

gMVP

0.26

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over