chr11-124397203-C-A

Position:

• chr11-124397203-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005467.2(OR8B3):​c.149G>T​(p.Gly50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G50S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: OR8B3 NM_001005467.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.13

Genes affected

OR8B3 (HGNC:8472): (olfactory receptor family 8 subfamily B member 3) 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]

OR8B2 (HGNC:8471): (olfactory receptor family 8 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0742774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR8B3	NM_001005467.2	c.149G>T	p.Gly50Val	missense_variant	2/2	ENST00000641139.1
OR8B3	XM_017017716.2	c.149G>T	p.Gly50Val	missense_variant	6/6
OR8B2	XM_017017535.3	c.-148+32G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR8B3	ENST00000641139.1	c.149G>T	p.Gly50Val	missense_variant	2/2		NM_001005467.2	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 148768 Hom.: 0 Cov.: 28 FAILED QC

Gnomad AFR AF: 0.0000256

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.: 39

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000672 AC: 1 AN: 148768 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 72564

Gnomad4 AFR AF: 0.0000256

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2024

The c.149G>T (p.G50V) alteration is located in exon 1 (coding exon 1) of the OR8B3 gene. This alteration results from a G to T substitution at nucleotide position 149, causing the glycine (G) at amino acid position 50 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	0.089
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.95
DANN	Benign	0.25
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.31	.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.090	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-3.0	.;D
REVEL	Benign	0.058
Sift	Benign	0.33	.;T
Sift4G	Benign	0.53	.;T
Polyphen		0.0030	B;B
Vest4		0.10
MutPred		0.26		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.20
MPC		0.68
ClinPred		0.054	T
GERP RS		2.5
Varity_R		0.060
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs369952528; hg19: chr11-124267099;