rs12065526

Variant names:

• chr1-247451105-G-A
• rs12065526
• NM_001004492.2:c.878C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004492.2(OR2B11):​c.878C>T​(p.Thr293Ile) variant causes a missense change. The variant allele was found at a frequency of 0.136 in 1,512,254 control chromosomes in the GnomAD database, including 15,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1965 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13231 hom.)
• Consequence: OR2B11 NM_001004492.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.67
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.048879E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2B11	NM_001004492.2	c.878C>T	p.Thr293Ile	missense_variant	Exon 2 of 2	ENST00000641149.2	NP_001004492.1
OR2B11	NR_169840.1	n.1532C>T		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2B11	ENST00000641149.2	c.878C>T	p.Thr293Ile	missense_variant	Exon 2 of 2		NM_001004492.2	ENSP00000492892.1
OR2B11	ENST00000641527.1	c.878C>T	p.Thr293Ile	missense_variant	Exon 3 of 3			ENSP00000493421.1
OR2B11	ENST00000641613.1	n.1532C>T		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23211 AN: 151986 Hom.: 1958 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.163

GnomAD2 exomes AF: 0.128 AC: 23036 AN: 179832 AF XY: 0.127

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.00144

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.134 AC: 182727 AN: 1360150 Hom.: 13231 Cov.: 31 AF XY: 0.132 AC XY: 88023 AN XY: 665800

African (AFR) AF: 0.203 AC: 6120 AN: 30098

American (AMR) AF: 0.158 AC: 4704 AN: 29706

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 3521 AN: 19946

East Asian (EAS) AF: 0.00239 AC: 93 AN: 38844

South Asian (SAS) AF: 0.0648 AC: 4523 AN: 69834

European-Finnish (FIN) AF: 0.122 AC: 6073 AN: 49902

Middle Eastern (MID) AF: 0.161 AC: 851 AN: 5270

European-Non Finnish (NFE) AF: 0.141 AC: 149175 AN: 1060628

Other (OTH) AF: 0.137 AC: 7667 AN: 55922

GnomAD4 genome AF: 0.153 AC: 23244 AN: 152104 Hom.: 1965 Cov.: 32 AF XY: 0.148 AC XY: 11041 AN XY: 74372

African (AFR) AF: 0.200 AC: 8271 AN: 41452

American (AMR) AF: 0.168 AC: 2570 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.0591 AC: 285 AN: 4826

European-Finnish (FIN) AF: 0.124 AC: 1311 AN: 10594

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9662 AN: 67990

Other (OTH) AF: 0.161 AC: 341 AN: 2112

Alfa AF: 0.146 Hom.: 5680

Bravo AF: 0.160

TwinsUK AF: 0.133 AC: 493

ALSPAC AF: 0.134 AC: 515

ESP6500AA AF: 0.200 AC: 880

ESP6500EA AF: 0.145 AC: 1249

ExAC AF: 0.123 AC: 14413

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.8
DANN	Benign	0.62
DEOGEN2	Benign	0.0011	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.48	.;.;T
MetaRNN	Benign	0.00090	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-3.8	N;N;N
PhyloP100		5.7
PrimateAI	Benign	0.26	T
PROVEAN	Benign	4.7	.;.;N
REVEL	Benign	0.12
Sift	Benign	1.0	.;.;T
Sift4G	Benign	1.0	.;.;T
Polyphen		0.0	B;B;B
Vest4		0.058
MPC		0.091
ClinPred		0.0036	T
GERP RS		5.1
Varity_R		0.046
gMVP		0.075
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12065526; hg19: chr1-247614407; COSMIC: COSV107389824; COSMIC: COSV107389824;