Variant 1-248145766-A-C 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.619A>C(p.Ile207Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,461,152 control chromosomes in the GnomAD database, including 4 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 0.0032 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

OR2M5
NM_001004690.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.86

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035918653).

BP6

Variant 1-248145766-A-C is Benign according to our data. Variant chr1-248145766-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2640250.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2M5	NM_001004690.1 linkuse as main transcript	c.619A>C	p.Ile207Leu	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.619A>C	p.Ile207Leu	missense_variant	1/1		NM_001004690.1	P1

Frequencies

GnomAD3 genomes

AF:

0.00316

AC:

477

AN:

151188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00946

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00309

Gnomad ASJ

AF:

0.00232

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0161

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.000759

AC:

190

AN:

250450

Hom.:

AF XY:

0.000635

AC XY:

AN XY:

135424

show subpopulations

Gnomad AFR exome

AF:

0.00497

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000343

AC:

501

AN:

1461152

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

240

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.00507

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00317

AC:

479

AN:

151300

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

221

AN XY:

73986

show subpopulations

Gnomad4 AFR

AF:

0.00946

Gnomad4 AMR

AF:

0.00315

Gnomad4 ASJ

AF:

0.00232

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.00152

Hom.:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00203

AC:

247

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

0.069

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.044

DANN

Benign

0.14

DEOGEN2

Benign

0.0031

Eigen

Benign

-2.7

Eigen_PC

Benign

-2.7

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.031

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

1.6

REVEL

Benign

0.034

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.096

MVP

0.030

MPC

0.023

ClinPred

0.0085

GERP RS

-6.6

Varity_R

0.039

gMVP

0.064

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