NM_001005276.1:c.944G>A

Variant names:

• chr7-99876090-C-T
• rs367594084
• NM_001005276.1:c.944G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005276.1(OR2AE1):​c.944G>A​(p.Arg315Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,602,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: OR2AE1 NM_001005276.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.176
• Publications: 2 publications found

Genes affected

OR2AE1 (HGNC:15087): (olfactory receptor family 2 subfamily AE member 1) 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05609867).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005276.1. 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
	OR2AE1	NM_001005276.1	MANE Select	c.944G>A	p.Arg315Gln	missense	Exon 1 of 1	NP_001005276.1	Q8NHA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2AE1	ENST00000316368.3	TSL:6 MANE Select	c.944G>A	p.Arg315Gln	missense	Exon 1 of 1	ENSP00000313936.2	Q8NHA4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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: 0.0000125 AC: 3 AN: 240614 AF XY: 0.0000154

Gnomad AFR exome AF: 0.000188

Gnomad AMR exome AF: 0.00

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: 0.00000896 AC: 13 AN: 1450160 Hom.: 0 Cov.: 33 AF XY: 0.0000111 AC XY: 8 AN XY: 720694

African (AFR) AF: 0.000152 AC: 5 AN: 32874

American (AMR) AF: 0.00 AC: 0 AN: 42716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25366

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 83832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000723 AC: 8 AN: 1107108

Other (OTH) AF: 0.00 AC: 0 AN: 59866

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74370

African (AFR) AF: 0.0000724 AC: 3 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

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	0.090
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.18
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.016
Sift	Benign	0.12	T
Sift4G	Uncertain	0.033	D
Polyphen		0.022	B
Vest4		0.20
MVP		0.14
MPC		0.041
ClinPred		0.017	T
GERP RS		0.13
Varity_R		0.10
gMVP		0.17
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: rs367594084; hg19: chr7-99473713;