NM_001004719.2:c.457T>C

Variant names:

• chr15-22081081-T-C
• rs750880271
• NM_001004719.2:c.457T>C

Variant summary

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

The NM_001004719.2(OR4M2):​c.457T>C​(p.Phe153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: OR4M2 NM_001004719.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• Publications: 4 publications found

Genes affected

OR4M2 (HGNC:15373): (olfactory receptor family 4 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]

OR4M2-OT1 (HGNC:56199): (OR4M2 overlapping transcript 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14353174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004719.2. 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
	OR4M2	NM_001004719.2	MANE Select	c.457T>C	p.Phe153Leu	missense	Exon 1 of 1	NP_001004719.2	Q8NGB6
	OR4M2-OT1	NR_110480.2		n.824-13432T>C		intron	N/A
	OR4M2-OT1	NR_110481.2		n.556-13432T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4M2	ENST00000614722.3	TSL:6 MANE Select	c.457T>C	p.Phe153Leu	missense	Exon 1 of 1	ENSP00000483239.1	Q8NGB6
	OR4M2-OT1	ENST00000639059.1	TSL:2	c.-9-13432T>C		intron	N/A	ENSP00000493899.1
	OR4M2	ENST00000638815.1	TSL:5	n.492T>C		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251450 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	Uncertain	0.54
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.1
Sift4G	Benign	0.13	T
Polyphen		0.74	P
Vest4		0.15
MutPred		0.46		Loss of methylation at R150 (P = 0.1122)
MVP		0.49
ClinPred		0.81	D
GERP RS		2.5
Varity_R		0.17
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs750880271; hg19: chr15-22369032;