rs1151687

Variant names:

• chr1-247588717-G-C
• rs1151687
• NM_001001915.1:c.358G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001915.1(OR2G2):​c.358G>C​(p.Val120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,613,842 control chromosomes in the GnomAD database, including 391,182 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.58 (29010 hom., cov: 31)
  • Exomes 𝑓: 0.70 (362172 hom.)
• Consequence: OR2G2 NM_001001915.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.999

Genes affected

OR2G2 (HGNC:15007): (olfactory receptor family 2 subfamily G member 2) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.532855E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2G2	NM_001001915.1	c.358G>C	p.Val120Leu	missense_variant	Exon 1 of 1	ENST00000320065.1	NP_001001915.1
LOC102724446	NR_188589.1	n.226-22766C>G		intron_variant	Intron 2 of 2
LOC102724446	NR_188590.1	n.438-22766C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2G2	ENST00000320065.1	c.358G>C	p.Val120Leu	missense_variant	Exon 1 of 1	6	NM_001001915.1	ENSP00000326349.1
ENSG00000236817	ENST00000435333.5	n.226-22766C>G		intron_variant	Intron 2 of 2	3
ENSG00000236817	ENST00000446347.1	n.438-22766C>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88055 AN: 151860 Hom.: 28995 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.615

GnomAD3 exomes AF: 0.689 AC: 172741 AN: 250850 Hom.: 61482 AF XY: 0.699 AC XY: 94733 AN XY: 135544

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.721

Gnomad ASJ exome AF: 0.755

Gnomad EAS exome AF: 0.798

Gnomad SAS exome AF: 0.756

Gnomad FIN exome AF: 0.675

Gnomad NFE exome AF: 0.704

Gnomad OTH exome AF: 0.705

GnomAD4 exome AF: 0.699 AC: 1022344 AN: 1461864 Hom.: 362172 Cov.: 62 AF XY: 0.703 AC XY: 510939 AN XY: 727228

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.716

Gnomad4 ASJ exome AF: 0.747

Gnomad4 EAS exome AF: 0.775

Gnomad4 SAS exome AF: 0.753

Gnomad4 FIN exome AF: 0.678

Gnomad4 NFE exome AF: 0.707

Gnomad4 OTH exome AF: 0.681

GnomAD4 genome AF: 0.580 AC: 88099 AN: 151978 Hom.: 29010 Cov.: 31 AF XY: 0.585 AC XY: 43424 AN XY: 74256

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.616

Alfa AF: 0.693 Hom.: 28000

Bravo AF: 0.566

TwinsUK AF: 0.701 AC: 2599

ALSPAC AF: 0.709 AC: 2732

ESP6500AA AF: 0.251 AC: 1107

ESP6500EA AF: 0.708 AC: 6090

ExAC AF: 0.678 AC: 82289

Asia WGS AF: 0.720 AC: 2505 AN: 3478

EpiCase AF: 0.703

EpiControl AF: 0.710

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	8.5e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.053
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.055	T
Polyphen		0.11	B
Vest4		0.084
MutPred		0.11		Loss of catalytic residue at V120 (P = 0.0719);
MPC		0.080
ClinPred		0.027	T
GERP RS		3.4
Varity_R		0.36
gMVP		0.13

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

Other links and lift over

dbSNP: rs1151687; hg19: chr1-247752019; COSMIC: COSV60739372;