1-248203299-G-A

Variant names:

• chr1-248203299-G-A
• rs141884297
• NM_001004689.2:c.232G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001004689.2(OR2M3):​c.232G>A​(p.Val78Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,613,980 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V78L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0072 (16 hom., cov: 31)
  • Exomes 𝑓: 0.00087 (8 hom.)
• Consequence: OR2M3 NM_001004689.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• Publications: 4 publications found

Genes affected

OR2M3 (HGNC:8269): (olfactory receptor family 2 subfamily M 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049291253).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0072 (1096/152130) while in subpopulation AFR AF = 0.0237 (984/41486). AF 95% confidence interval is 0.0225. There are 16 homozygotes in GnomAd4. There are 536 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004689.2. 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
	OR2M3	NM_001004689.2	MANE Select	c.232G>A	p.Val78Ile	missense	Exon 2 of 2	NP_001004689.1	Q8NG83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2M3	ENST00000641626.1	MANE Select	c.232G>A	p.Val78Ile	missense	Exon 2 of 2	ENSP00000492981.1	Q8NG83
	OR2M3	ENST00000456743.3	TSL:6	c.232G>A	p.Val78Ile	missense	Exon 1 of 1	ENSP00000389625.1	Q8NG83

Frequencies

GnomAD3 genomes AF: 0.00717 AC: 1090 AN: 152012 Hom.: 16 Cov.: 31

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00505

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00957

GnomAD2 exomes AF: 0.00214 AC: 537 AN: 251328 AF XY: 0.00162

Gnomad AFR exome AF: 0.0268

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.000870 AC: 1272 AN: 1461850 Hom.: 8 Cov.: 30 AF XY: 0.000831 AC XY: 604 AN XY: 727226

African (AFR) AF: 0.0236 AC: 791 AN: 33474

American (AMR) AF: 0.00190 AC: 85 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86254

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

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5762

European-Non Finnish (NFE) AF: 0.000205 AC: 228 AN: 1111990

Other (OTH) AF: 0.00230 AC: 139 AN: 60396

GnomAD4 genome AF: 0.00720 AC: 1096 AN: 152130 Hom.: 16 Cov.: 31 AF XY: 0.00721 AC XY: 536 AN XY: 74364

African (AFR) AF: 0.0237 AC: 984 AN: 41486

American (AMR) AF: 0.00504 AC: 77 AN: 15268

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68004

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.00103 Hom.: 0

Bravo AF: 0.00837

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0225 AC: 99

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00242 AC: 294

EpiCase AF: 0.000382

EpiControl AF: 0.000474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
PhyloP100		-3.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.058
Sift	Benign	0.062	T
Sift4G	Benign	0.13	T
Polyphen		0.58	P
Vest4		0.040
MVP		0.20
MPC		0.059
ClinPred		0.0065	T
GERP RS		2.4
PromoterAI		-0.014	Neutral
Varity_R		0.038
gMVP		0.037
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: rs141884297; hg19: chr1-248366601; COSMIC: COSV71759166;