chr1-247606087-C-G

Variant names:

• chr1-247606087-C-G
• rs546158623
• NM_001001914.1:c.502C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001914.1(OR2G3):​c.502C>G​(p.Leu168Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,614,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L168F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: OR2G3 NM_001001914.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.371
• Publications: 1 publications found

Genes affected

OR2G3 (HGNC:15008): (olfactory receptor family 2 subfamily G member 3) 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]

ENSG00000236817 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015866548).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001914.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2G3	NM_001001914.1	MANE Select	c.502C>G	p.Leu168Val	missense	Exon 1 of 1	NP_001001914.1	Q8NGZ4
	LOC102724446	NR_188589.1		n.225+29768G>C		intron	N/A
	LOC102724446	NR_188590.1		n.437+29768G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2G3	ENST00000320002.3	TSL:6 MANE Select	c.502C>G	p.Leu168Val	missense	Exon 1 of 1	ENSP00000326301.2	Q8NGZ4
	ENSG00000236817	ENST00000435333.6	TSL:3	n.294+29768G>C		intron	N/A
	ENSG00000236817	ENST00000446347.1	TSL:2	n.437+29768G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251406 AF XY: 0.0000662

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461892 Hom.: 0 Cov.: 34 AF XY: 0.0000179 AC XY: 13 AN XY: 727248

African (AFR) AF: 0.000896 AC: 30 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74478

African (AFR) AF: 0.000650 AC: 27 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000215

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.1
DANN	Benign	0.40
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.37
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Benign	0.17	T
Sift4G	Benign	0.071	T
Polyphen		0.0060	B
Vest4		0.016
MVP		0.10
MPC		0.065
ClinPred		0.13	T
GERP RS		-3.3
Varity_R		0.18
gMVP		0.024
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs546158623; hg19: chr1-247769389;