Variant rs41304157 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2M5	NM_001004690.1 linkuse as main transcript	c.710C>A	p.Ala237Asp	missense_variant	1/1	ENST00000366476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2M5	ENST00000366476.1 linkuse as main transcript	c.710C>A	p.Ala237Asp	missense_variant	1/1		NM_001004690.1	P1

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

GnomAD3 exomes

AF:

0.0203

AC:

5102

AN:

251334

Hom.:

AF XY:

0.0201

AC XY:

2732

AN XY:

135842

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 SAS exome

AF:

0.00229

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

Gnomad4 AFR exome

AF:

0.0245

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.00421

Gnomad4 EAS exome

AF:

0.0133

Gnomad4 SAS exome

AF:

0.00276

Gnomad4 FIN exome

AF:

0.0298

Gnomad4 NFE exome

AF:

0.0308

Gnomad4 OTH exome

AF:

0.0255

GnomAD4 genome

AF:

0.0237

AC:

3615

AN:

152246

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

1685

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00849

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.0286

Gnomad4 NFE

AF:

0.0303

Gnomad4 OTH

AF:

0.0208

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

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

MutationTaster

Benign

0.60

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

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