11-58422337-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5B2	NM_001005566.3	c.925C>G	p.Leu309Val	missense_variant	Exon 3 of 3	ENST00000641342.2	NP_001005566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5B2	ENST00000641342.2	c.925C>G	p.Leu309Val	missense_variant	Exon 3 of 3		NM_001005566.3	ENSP00000493419.1
OR5B2	ENST00000302581.2	c.925C>G	p.Leu309Val	missense_variant	Exon 1 of 1	6		ENSP00000303076.2

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

GnomAD3 exomes AF: 0.000280 AC: 69 AN: 246222 Hom.: 0 AF XY: 0.000248 AC XY: 33 AN XY: 133030

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000685

Gnomad4 ASJ exome AF: 0.00692

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000273

Gnomad4 OTH exome AF: 0.000637

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000478

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.925C>G (p.L309V) alteration is located in exon 1 (coding exon 1) of the OR5B2 gene. This alteration results from a C to G substitution at nucleotide position 925, causing the leucine (L) at amino acid position 309 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N
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;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs373422198; hg19: chr11-58189810;