dbSNP rs41304157: OR2M5:p.Ala237Asp (chr1-248145857-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001004690.1(OR2M5):c.710C>A(p.Ala237Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 1,613,502 control chromosomes in the GnomAD database, including 660 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A237S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.024 ( 43 hom., cov: 32)

Exomes 𝑓: 0.027 ( 617 hom. )

Consequence

OR2M5
NM_001004690.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28

Publications

8 publications found

Variant links:

Genes affected

OR2M5 (HGNC:19576): (olfactory receptor family 2 subfamily M 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]

OR2M5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006318927).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0237 (3615/152246) while in subpopulation NFE AF = 0.0303 (2062/68008). AF 95% confidence interval is 0.0292. There are 43 homozygotes in GnomAd4. There are 1685 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2M5	NM_001004690.1 link	c.710C>A	p.Ala237Asp	missense_variant	Exon 1 of 1	ENST00000366476.1	NP_001004690.1	A3KFT3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2M5	ENST00000366476.1 link	c.710C>A	p.Ala237Asp	missense_variant	Exon 1 of 1	6	NM_001004690.1	ENSP00000355432.1		A3KFT3

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3614

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00847

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0286

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0303

Gnomad OTH

AF:

0.0211

GnomAD2 exomes

AF:

0.0203

AC:

5102

AN:

251334

AF XY:

0.0201

show subpopulations

Gnomad AFR exome

AF:

0.0248

Gnomad AMR exome

AF:

0.00943

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.00843

Gnomad FIN exome

AF:

0.0281

Gnomad NFE exome

AF:

0.0296

Gnomad OTH exome

AF:

0.0223

GnomAD4 exome

AF:

0.0271

AC:

39593

AN:

1461256

Hom.:

617

Cov.:

AF XY:

0.0263

AC XY:

19152

AN XY:

726946

show subpopulations

African (AFR)

AF:

0.0245

AC:

821

AN:

33454

American (AMR)

AF:

0.0102

AC:

454

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00421

AC:

110

AN:

26126

East Asian (EAS)

AF:

0.0133

AC:

528

AN:

39698

South Asian (SAS)

AF:

0.00276

AC:

238

AN:

86230

European-Finnish (FIN)

AF:

0.0298

AC:

1591

AN:

53420

Middle Eastern (MID)

AF:

0.00989

AC:

AN:

5458

European-Non Finnish (NFE)

AF:

0.0308

AC:

34261

AN:

1111832

Other (OTH)

AF:

0.0255

AC:

1536

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

2923

5846

8769

11692

14615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1282

2564

3846

5128

6410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0237

AC:

3615

AN:

152246

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

1685

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0223

AC:

928

AN:

41540

American (AMR)

AF:

0.0126

AC:

193

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.00849

AC:

AN:

5184

South Asian (SAS)

AF:

0.00270

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0286

AC:

303

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0303

AC:

2062

AN:

68008

Other (OTH)

AF:

0.0208

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

181

362

544

725

906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0265

Hom.:

Bravo

AF:

0.0229

TwinsUK

AF:

0.0291

AC:

108

ALSPAC

AF:

0.0361

AC:

139

ESP6500AA

AF:

0.0243

AC:

107

ESP6500EA

AF:

0.0258

AC:

222

ExAC

AF:

0.0209

AC:

2542

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0303

EpiControl

AF:

0.0273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0063

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.6

PhyloP100

2.3

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.22

MPC

0.18

ClinPred

0.076

GERP RS

3.0

Varity_R

0.75

gMVP

0.31

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over