rs4916104

Variant names:

• chr1-248180688-T-C
• rs4916104
• NM_001004688.2:c.703T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-248180688-T-C
• chr1-248180688-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001004688.2(OR2M2):​c.703T>C​(p.Cys235Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,612,124 control chromosomes in the GnomAD database, including 326,238 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C235Y) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.62 (29369 hom., cov: 32)
  • Exomes 𝑓: 0.64 (296869 hom.)
• Consequence: OR2M2 NM_001004688.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.27
• Publications: 23 publications found

Genes affected

OR2M2 (HGNC:8268): (olfactory receptor family 2 subfamily M 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.7955297E-6).
• BP6: Variant 1-248180688-T-C is Benign according to our data. Variant chr1-248180688-T-C is described in ClinVar as Benign. ClinVar VariationId is 767775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004688.2. 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
	OR2M2	NM_001004688.2	MANE Select	c.703T>C	p.Cys235Arg	missense	Exon 2 of 2	NP_001004688.1	A0A126GWI7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2M2	ENST00000641836.1	MANE Select	c.703T>C	p.Cys235Arg	missense	Exon 2 of 2	ENSP00000493201.1	Q96R28
	OR2M2	ENST00000641211.1		c.703T>C	p.Cys235Arg	missense	Exon 3 of 3	ENSP00000492974.1	Q96R28

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94122 AN: 151942 Hom.: 29337 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.639

GnomAD2 exomes AF: 0.614 AC: 149832 AN: 244222 AF XY: 0.619

Gnomad AFR exome AF: 0.601

Gnomad AMR exome AF: 0.596

Gnomad ASJ exome AF: 0.555

Gnomad EAS exome AF: 0.432

Gnomad FIN exome AF: 0.635

Gnomad NFE exome AF: 0.654

Gnomad OTH exome AF: 0.633

GnomAD4 exome AF: 0.636 AC: 928405 AN: 1460064 Hom.: 296869 Cov.: 85 AF XY: 0.635 AC XY: 461505 AN XY: 726396

African (AFR) AF: 0.603 AC: 20162 AN: 33414

American (AMR) AF: 0.599 AC: 26770 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 14563 AN: 26128

East Asian (EAS) AF: 0.438 AC: 17408 AN: 39700

South Asian (SAS) AF: 0.606 AC: 52199 AN: 86184

European-Finnish (FIN) AF: 0.637 AC: 34046 AN: 53418

Middle Eastern (MID) AF: 0.623 AC: 2882 AN: 4624

European-Non Finnish (NFE) AF: 0.650 AC: 722329 AN: 1111652

Other (OTH) AF: 0.632 AC: 38046 AN: 60236

GnomAD4 genome AF: 0.619 AC: 94197 AN: 152060 Hom.: 29369 Cov.: 32 AF XY: 0.618 AC XY: 45904 AN XY: 74312

African (AFR) AF: 0.596 AC: 24715 AN: 41468

American (AMR) AF: 0.620 AC: 9464 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1935 AN: 3472

East Asian (EAS) AF: 0.427 AC: 2202 AN: 5162

South Asian (SAS) AF: 0.606 AC: 2922 AN: 4818

European-Finnish (FIN) AF: 0.629 AC: 6646 AN: 10574

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44199 AN: 67986

Other (OTH) AF: 0.636 AC: 1343 AN: 2112

Alfa AF: 0.634 Hom.: 13166

Bravo AF: 0.617

ESP6500AA AF: 0.571 AC: 2517

ESP6500EA AF: 0.627 AC: 5393

ExAC AF: 0.611 AC: 74202

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.90	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.17
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00052	N
LIST_S2	Benign	0.0062	T
MetaRNN	Benign	0.0000038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-3.3
PrimateAI	Benign	0.17	T
PROVEAN	Benign	5.1	N
REVEL	Benign	0.020
Sift	Benign	0.52	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.0090
MPC		0.19
ClinPred		0.0042	T
GERP RS		1.1
Varity_R		0.074
gMVP		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs4916104; hg19: chr1-248343990; COSMIC: COSV62897713;