chr15-22081074-G-A

Variant names:

• chr15-22081074-G-A
• rs367552249
• NM_001004719.2:c.450G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001004719.2(OR4M2):​c.450G>A​(p.Arg150Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4M2 NM_001004719.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.96
• Publications: 3 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-3.96 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4M2	NM_001004719.2	c.450G>A	p.Arg150Arg	synonymous_variant	Exon 1 of 1	ENST00000614722.3	NP_001004719.2
OR4M2-OT1	NR_110480.2	n.824-13439G>A		intron_variant	Intron 7 of 8
OR4M2-OT1	NR_110481.2	n.556-13439G>A		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4M2	ENST00000614722.3	c.450G>A	p.Arg150Arg	synonymous_variant	Exon 1 of 1	6	NM_001004719.2	ENSP00000483239.1
OR4M2-OT1	ENST00000639059.1	c.-9-13439G>A		intron_variant	Intron 6 of 6	2		ENSP00000493899.1
OR4M2	ENST00000638815.1	n.485G>A		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251412 AF XY: 0.00

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 80802 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 43548

African (AFR) AF: 0.00 AC: 0 AN: 6112

American (AMR) AF: 0.00 AC: 0 AN: 3146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2404

East Asian (EAS) AF: 0.00 AC: 0 AN: 2482

South Asian (SAS) AF: 0.00 AC: 0 AN: 12818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 530

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 43968

Other (OTH) AF: 0.00 AC: 0 AN: 5232

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.61
PhyloP100		-4.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs367552249; hg19: chr15-22369025; COSMIC: COSV106469223;