rs12279895

Variant names:

• chr11-58402523-T-C
• rs12279895
• NM_001005469.2:c.887A>G

Variant summary

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

The NM_001005469.2(OR5B3):​c.887A>G​(p.Lys296Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,605,970 control chromosomes in the GnomAD database, including 99,988 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.33 (8304 hom., cov: 32)
  • Exomes 𝑓: 0.35 (91684 hom.)
• Consequence: OR5B3 NM_001005469.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 29 publications found

Genes affected

OR5B3 (HGNC:8324): (olfactory receptor family 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019082725).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5B3	NM_001005469.2	c.887A>G	p.Lys296Arg	missense_variant	Exon 2 of 2	ENST00000641865.1	NP_001005469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5B3	ENST00000641865.1	c.887A>G	p.Lys296Arg	missense_variant	Exon 2 of 2		NM_001005469.2	ENSP00000493217.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49989 AN: 151916 Hom.: 8305 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.304

GnomAD2 exomes AF: 0.312 AC: 78260 AN: 251074 AF XY: 0.313

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.321

GnomAD4 exome AF: 0.349 AC: 507755 AN: 1453936 Hom.: 91684 Cov.: 35 AF XY: 0.348 AC XY: 251674 AN XY: 723740

African (AFR) AF: 0.325 AC: 10822 AN: 33268

American (AMR) AF: 0.230 AC: 10276 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8739 AN: 26088

East Asian (EAS) AF: 0.168 AC: 6659 AN: 39680

South Asian (SAS) AF: 0.284 AC: 24480 AN: 86140

European-Finnish (FIN) AF: 0.335 AC: 17868 AN: 53412

Middle Eastern (MID) AF: 0.313 AC: 1799 AN: 5754

European-Non Finnish (NFE) AF: 0.369 AC: 407152 AN: 1104746

Other (OTH) AF: 0.332 AC: 19960 AN: 60176

GnomAD4 genome AF: 0.329 AC: 50004 AN: 152034 Hom.: 8304 Cov.: 32 AF XY: 0.325 AC XY: 24125 AN XY: 74308

African (AFR) AF: 0.324 AC: 13445 AN: 41456

American (AMR) AF: 0.262 AC: 4006 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1202 AN: 3472

East Asian (EAS) AF: 0.150 AC: 779 AN: 5178

South Asian (SAS) AF: 0.300 AC: 1441 AN: 4806

European-Finnish (FIN) AF: 0.333 AC: 3512 AN: 10556

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24584 AN: 67962

Other (OTH) AF: 0.302 AC: 638 AN: 2114

Alfa AF: 0.348 Hom.: 25202

Bravo AF: 0.321

TwinsUK AF: 0.373 AC: 1382

ALSPAC AF: 0.378 AC: 1457

ESP6500AA AF: 0.328 AC: 1442

ESP6500EA AF: 0.360 AC: 3093

ExAC AF: 0.319 AC: 38693

Asia WGS AF: 0.264 AC: 917 AN: 3478

EpiCase AF: 0.354

EpiControl AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.75	.;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	M;M
PhyloP100		-0.056
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-2.5	.;N
REVEL	Benign	0.041
Sift	Uncertain	0.020	.;D
Sift4G	Uncertain	0.0090	.;D
Polyphen		0.34	B;B
Vest4		0.044
MPC		0.040
ClinPred		0.011	T
GERP RS		3.9
Varity_R		0.24
gMVP		0.073
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12279895; hg19: chr11-58169996; COSMIC: COSV58676611;