Genetic Variant NM_001004691.1:c.826G>C (chr1-248323743-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004691.1(OR2M7):c.826G>C(p.Val276Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,613,268 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

OR2M7
NM_001004691.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.07

Variant links:

Genes affected

OR2M7 (HGNC:19594): (olfactory receptor family 2 subfamily M member 7) 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]

OR2M7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02905941).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2M7	NM_001004691.1 link	c.826G>C	p.Val276Leu	missense_variant	Exon 1 of 1	ENST00000317965.3	NP_001004691.1	Q8NG81A0A126GVZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2M7	ENST00000317965.3 link	c.826G>C	p.Val276Leu	missense_variant	Exon 1 of 1	6	NM_001004691.1	ENSP00000324557.2		Q8NG81

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000159

AC:

AN:

250858

Hom.:

AF XY:

0.000207

AC XY:

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000203

AC:

297

AN:

1461048

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

157

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000238

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000164

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000447

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.826G>C (p.V276L) alteration is located in exon 1 (coding exon 1) of the OR2M7 gene. This alteration results from a G to C substitution at nucleotide position 826, causing the valine (V) at amino acid position 276 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.7

DANN

Benign

0.85

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.79

M_CAP

Benign

0.00060

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.27

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.2

REVEL

Benign

0.023

Sift

Benign

0.13

Sift4G

Benign

0.17

Polyphen

0.57

Vest4

0.021

MutPred

0.40

Loss of methylation at K272 (P = 0.0939);

MVP

0.18

MPC

0.051

ClinPred

0.034

GERP RS

0.53

Varity_R

0.12

gMVP

0.037

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over