11-58422777-A-C

Variant names:

• chr11-58422777-A-C
• rs1244098965
• NM_001005566.3:c.485T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001005566.3(OR5B2):​c.485T>G​(p.Phe162Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: OR5B2 NM_001005566.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4096417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5B2	NM_001005566.3	c.485T>G	p.Phe162Cys	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.485T>G	p.Phe162Cys	missense_variant	Exon 3 of 3		NM_001005566.3	ENSP00000493419.1
OR5B2	ENST00000302581.2	c.485T>G	p.Phe162Cys	missense_variant	Exon 1 of 1	6		ENSP00000303076.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74326

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.485T>G (p.F162C) alteration is located in exon 1 (coding exon 1) of the OR5B2 gene. This alteration results from a T to G substitution at nucleotide position 485, causing the phenylalanine (F) at amino acid position 162 to be replaced by a cysteine (C). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	0.12
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.95	.;D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Benign	0.25	T
PROVEAN	Pathogenic	-7.5	.;D
REVEL	Benign	0.043
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0010	.;D
Polyphen		1.0	D;D
Vest4		0.44
MutPred		0.56		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.50
MPC		0.018
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.76
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs1244098965; hg19: chr11-58190250;