1-248239679-T-C

Variant names:

• chr1-248239679-T-C
• rs372109202
• NM_017504.2:c.751T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017504.2(OR2M4):​c.751T>C​(p.Tyr251His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: OR2M4 NM_017504.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.807
• Publications: 2 publications found

Genes affected

OR2M4 (HGNC:8270): (olfactory receptor family 2 subfamily M member 4) 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11430329).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017504.2. 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
	OR2M4	NM_017504.2	MANE Select	c.751T>C	p.Tyr251His	missense	Exon 2 of 2	NP_059974.1	A0A126GV73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2M4	ENST00000641868.1	MANE Select	c.751T>C	p.Tyr251His	missense	Exon 2 of 2	ENSP00000492992.1	Q96R27

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000749

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: 0.0000597 AC: 15 AN: 251128 AF XY: 0.0000590

Gnomad AFR exome AF: 0.000923

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: 0.0000144 AC: 21 AN: 1461868 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 727238

African (AFR) AF: 0.000538 AC: 18 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

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

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74460

African (AFR) AF: 0.000746 AC: 31 AN: 41536

American (AMR) AF: 0.00 AC: 0 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000296 Hom.: 0

Bravo AF: 0.000189

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000576 AC: 7

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	0.30
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.072
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.81
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.27
MVP		0.59
MPC		0.37
ClinPred		0.40	T
GERP RS		3.3
Varity_R		0.25
gMVP		0.22
Mutation Taster		=94/6	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: rs372109202; hg19: chr1-248402981;