chr1-247588717-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -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	ENST00000435333.6	n.295-22766C>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

GnomAD2 exomes AF: 0.689 AC: 172741 AN: 250850 AF XY: 0.699

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 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

African (AFR) AF: 0.227 AC: 7590 AN: 33480

American (AMR) AF: 0.716 AC: 32040 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 19531 AN: 26132

East Asian (EAS) AF: 0.775 AC: 30779 AN: 39700

South Asian (SAS) AF: 0.753 AC: 64973 AN: 86256

European-Finnish (FIN) AF: 0.678 AC: 36237 AN: 53416

Middle Eastern (MID) AF: 0.635 AC: 3660 AN: 5766

European-Non Finnish (NFE) AF: 0.707 AC: 786386 AN: 1111998

Other (OTH) AF: 0.681 AC: 41148 AN: 60392

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

African (AFR) AF: 0.244 AC: 10114 AN: 41476

American (AMR) AF: 0.676 AC: 10315 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2582 AN: 3466

East Asian (EAS) AF: 0.780 AC: 4021 AN: 5154

South Asian (SAS) AF: 0.760 AC: 3660 AN: 4818

European-Finnish (FIN) AF: 0.672 AC: 7089 AN: 10544

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.708 AC: 48117 AN: 67946

Other (OTH) AF: 0.616 AC: 1299 AN: 2110

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
PhyloP100		1.0
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
PromoterAI		-0.0076	Neutral
Varity_R		0.36
gMVP		0.13
Mutation Taster		=100/0	polymorphism (auto)

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