Variant 1-248145742-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004690.1(OR2M5):c.595C>A(p.Leu199Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000648 in 1,611,126 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 10 hom. )

Consequence

OR2M5
NM_001004690.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00427109).

BP6

Variant 1-248145742-C-A is Benign according to our data. Variant chr1-248145742-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640249.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2M5	NM_001004690.1 linkuse as main transcript	c.595C>A	p.Leu199Ile	missense_variant	1/1	ENST00000366476.1	NP_001004690.1	A3KFT3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2M5	ENST00000366476.1 linkuse as main transcript	c.595C>A	p.Leu199Ile	missense_variant	1/1	6	NM_001004690.1	ENSP00000355432.1		A3KFT3

Frequencies

GnomAD3 genomes

AF:

0.00288

AC:

435

AN:

151220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00848

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00283

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.00164

AC:

411

AN:

250824

Hom.:

AF XY:

0.00131

AC XY:

178

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.00284

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000662

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.000415

AC:

606

AN:

1459792

Hom.:

Cov.:

AF XY:

0.000386

AC XY:

280

AN XY:

726322

show subpopulations

Gnomad4 AFR exome

AF:

0.00697

Gnomad4 AMR exome

AF:

0.00191

Gnomad4 ASJ exome

AF:

0.00158

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00289

AC:

438

AN:

151334

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

199

AN XY:

74004

show subpopulations

Gnomad4 AFR

AF:

0.00853

Gnomad4 AMR

AF:

0.00283

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.00189

Hom.:

ExAC

AF:

0.00230

AC:

279

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

OR2M5: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.052

DANN

Benign

0.82

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

PrimateAI

Benign

0.21

PROVEAN

Benign

0.020

REVEL

Benign

0.016

Sift

Benign

0.51

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.12

MVP

0.030

MPC

0.024

ClinPred

0.0011

GERP RS

-7.0

Varity_R

0.037

gMVP

0.022

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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