rs373422198

Variant names:

• chr11-58422337-G-C
• rs373422198
• NM_001005566.3:c.925C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-58422337-G-C
• chr11-58422337-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005566.3(OR5B2):​c.925C>G​(p.Leu309Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,597,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: OR5B2 NM_001005566.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.230
• Publications: 2 publications found

Genes affected

OR5B2 (HGNC:8323): (olfactory receptor family 5 subfamily B 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.007534772).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005566.3. 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
	OR5B2	NM_001005566.3	MANE Select	c.925C>G	p.Leu309Val	missense	Exon 3 of 3	NP_001005566.1	Q96R09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5B2	ENST00000641342.2	MANE Select	c.925C>G	p.Leu309Val	missense	Exon 3 of 3	ENSP00000493419.1	Q96R09
	OR5B2	ENST00000302581.2	TSL:6	c.925C>G	p.Leu309Val	missense	Exon 1 of 1	ENSP00000303076.2	Q96R09

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000280 AC: 69 AN: 246222 AF XY: 0.000248

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000297

Gnomad ASJ exome AF: 0.00621

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000449

Gnomad OTH exome AF: 0.000503

GnomAD4 exome AF: 0.000172 AC: 249 AN: 1445016 Hom.: 0 Cov.: 28 AF XY: 0.000167 AC XY: 120 AN XY: 717026

African (AFR) AF: 0.00 AC: 0 AN: 32964

American (AMR) AF: 0.0000685 AC: 3 AN: 43774

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 178 AN: 25736

East Asian (EAS) AF: 0.00 AC: 0 AN: 39390

South Asian (SAS) AF: 0.00 AC: 0 AN: 85298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.0000273 AC: 30 AN: 1099324

Other (OTH) AF: 0.000637 AC: 38 AN: 59634

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152080 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74246

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.0000656 AC: 1 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68012

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000901 Hom.: 0

Bravo AF: 0.000166

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000222 AC: 27

EpiCase AF: 0.00

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	Benign	0.075
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.76
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.0075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.23
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.023
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.14	T
Polyphen		0.035	B
Vest4		0.089
MVP		0.040
MPC		0.0050
ClinPred		0.051	T
GERP RS		-3.9
Varity_R		0.085
gMVP		0.042
Mutation Taster		=98/2	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: rs373422198; hg19: chr11-58189810;