NM_001386033.1:c.394C>G

Variant names:

• chr14-20197831-C-G
• rs1301791652
• NM_001386033.1:c.394C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001386033.1(OR11G2):​c.394C>G​(p.Arg132Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,870 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R132Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OR11G2 NM_001386033.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.34
• Publications: 0 publications found

Genes affected

OR11G2 (HGNC:15346): (olfactory receptor family 11 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23116308).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386033.1. 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
	OR11G2	NM_001386033.1	MANE Select	c.394C>G	p.Arg132Gly	missense	Exon 2 of 2	NP_001372962.1	A0A126GWS8
	OR11G2	NM_001005503.2		c.394C>G	p.Arg132Gly	missense	Exon 2 of 2	NP_001005503.2	A0A126GWS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR11G2	ENST00000641879.2	MANE Select	c.394C>G	p.Arg132Gly	missense	Exon 2 of 2	ENSP00000493427.1	A0A126GWS8
	OR11G2	ENST00000641682.1		c.394C>G	p.Arg132Gly	missense	Exon 2 of 2	ENSP00000493171.1	A0A126GWS8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461870 Hom.: 0 Cov.: 44 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 53412

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.4
DANN	Benign	0.93
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.098	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-5.3
PrimateAI	Benign	0.17	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.096
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.049	D
Polyphen		0.51	P
Vest4		0.22
MutPred		0.45		Gain of catalytic residue at A163 (P = 0.0019)
MVP		0.25
MPC		0.22
ClinPred		0.36	T
GERP RS		-2.4
Varity_R		0.48
gMVP		0.18
Mutation Taster		=97/3	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: rs1301791652; hg19: chr14-20665990;