1-247451270-C-A

Variant summary

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

The NM_001004492.2(OR2B11):c.713G>T(p.Arg238Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. R238Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OR2B11 NM_001004492.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.837

Genes affected

OR2B11 (HGNC:31249): (olfactory receptor family 2 subfamily B member 11) 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=0.11621472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2B11	NM_001004492.2	c.713G>T	p.Arg238Leu	missense_variant	2/2	ENST00000641149.2
OR2B11	NR_169840.1	n.1367G>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2B11	ENST00000641149.2	c.713G>T	p.Arg238Leu	missense_variant	2/2		NM_001004492.2	P1
OR2B11	ENST00000641527.1	c.713G>T	p.Arg238Leu	missense_variant	3/3			P1
OR2B11	ENST00000641613.1	n.1367G>T		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251160 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135706

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461490 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726986

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000227

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

Jan 23, 2024

The c.713G>T (p.R238L) alteration is located in exon 1 (coding exon 1) of the OR2B11 gene. This alteration results from a G to T substitution at nucleotide position 713, causing the arginine (R) at amino acid position 238 to be replaced by a leucine (L). 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	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	18
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0091	T;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.18	N
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.1	M;M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
Polyphen		0.038	B;B;B
Vest4		0.46
MutPred		0.54		Loss of methylation at R238 (P = 0.0086);Loss of methylation at R238 (P = 0.0086);Loss of methylation at R238 (P = 0.0086);
MVP		0.30
MPC		0.52
ClinPred		0.87	D
GERP RS		2.2
Varity_R		0.17
gMVP		0.48

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: rs149924080; hg19: chr1-247614572;