rs370445398

Variant names:

• chr15-22080691-G-A
• rs370445398
• NM_001004719.2:c.67G>A

Variant summary

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

The NM_001004719.2(OR4M2):​c.67G>A​(p.Val23Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00014 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4M2 NM_001004719.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.365
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031387508).

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.67G>A	p.Val23Ile	missense	Exon 1 of 1	NP_001004719.2	Q8NGB6
	OR4M2-OT1	NR_110480.2		n.824-13822G>A		intron	N/A
	OR4M2-OT1	NR_110481.2		n.556-13822G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4M2	ENST00000614722.3	TSL:6 MANE Select	c.67G>A	p.Val23Ile	missense	Exon 1 of 1	ENSP00000483239.1	Q8NGB6
	OR4M2-OT1	ENST00000639059.1	TSL:2	c.-9-13822G>A		intron	N/A	ENSP00000493899.1
	OR4M2	ENST00000638815.1	TSL:5	n.267+43G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 2836 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.0000119 AC: 3 AN: 251260 AF XY: 0.00

Gnomad AFR exome AF: 0.000185

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000142 AC: 3 AN: 21100 Hom.: 1 Cov.: 0 AF XY: 0.000183 AC XY: 2 AN XY: 10926

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000553 AC: 1 AN: 1808

American (AMR) AF: 0.00313 AC: 2 AN: 640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 696

East Asian (EAS) AF: 0.00 AC: 0 AN: 670

South Asian (SAS) AF: 0.00 AC: 0 AN: 1254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 178

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 13248

Other (OTH) AF: 0.00 AC: 0 AN: 1666

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2836 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1276

African (AFR) AF: 0.00 AC: 0 AN: 1536

American (AMR) AF: 0.00 AC: 0 AN: 152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 36

East Asian (EAS) AF: 0.00 AC: 0 AN: 32

South Asian (SAS) AF: 0.00 AC: 0 AN: 132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840

Other (OTH) AF: 0.00 AC: 0 AN: 38

Alfa AF: 0.0000843 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

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	0.084
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.73
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.29	N
PhyloP100		-0.36
Sift4G	Benign	0.34	T
Polyphen		0.0090	B
Vest4		0.30
MVP		0.23
ClinPred		0.013	T
GERP RS		1.6
PromoterAI		0.013	Neutral
Varity_R		0.014
gMVP		0.069

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: rs370445398; hg19: chr15-22368642;