rs202009987

Variant names:

• chr19-9093449-G-A
• rs202009987
• NM_001004456.2:c.205G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004456.2(OR1M1):​c.205G>A​(p.Val69Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,610,792 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: OR1M1 NM_001004456.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.60
• Publications: 5 publications found

Genes affected

OR1M1 (HGNC:8220): (olfactory receptor family 1 subfamily M 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027991533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004456.2. 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
	OR1M1	NM_001004456.2	MANE Select	c.205G>A	p.Val69Ile	missense	Exon 2 of 2	NP_001004456.1	Q8NGA1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1M1	ENST00000641627.1	MANE Select	c.205G>A	p.Val69Ile	missense	Exon 2 of 2	ENSP00000493107.1	Q8NGA1
	OR1M1	ENST00000429566.3	TSL:6	c.205G>A	p.Val69Ile	missense	Exon 1 of 1	ENSP00000401966.2	Q8NGA1

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152010 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000163 AC: 41 AN: 251346 AF XY: 0.000214

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000125 AC: 182 AN: 1458664 Hom.: 1 Cov.: 33 AF XY: 0.000167 AC XY: 121 AN XY: 725868

African (AFR) AF: 0.000120 AC: 4 AN: 33414

American (AMR) AF: 0.000112 AC: 5 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.00120 AC: 103 AN: 86178

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

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5760

European-Non Finnish (NFE) AF: 0.0000496 AC: 55 AN: 1109096

Other (OTH) AF: 0.000149 AC: 9 AN: 60294

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152128 Hom.: 0 Cov.: 30 AF XY: 0.000108 AC XY: 8 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41522

American (AMR) AF: 0.000131 AC: 2 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.000173 AC: 21

EpiCase AF: 0.000273

EpiControl AF: 0.000119

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	0.13
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-3.6
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.075
Sift	Benign	0.082	T
Sift4G	Benign	0.079	T
Polyphen		0.99	D
Vest4		0.035
MVP		0.15
MPC		0.18
ClinPred		0.080	T
GERP RS		-0.91
PromoterAI		0.013	Neutral
Varity_R		0.027
gMVP		0.14
Mutation Taster		=99/1	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: rs202009987; hg19: chr19-9204125; COSMIC: COSV70036689;