11-58402818-T-C

Variant names:

• chr11-58402818-T-C
• rs11229410
• NM_001005469.2:c.592A>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.592A>G​(p.Ile198Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,612,694 control chromosomes in the GnomAD database, including 100,166 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 (8317 hom., cov: 32)
  • Exomes 𝑓: 0.35 (91849 hom.)
• Consequence: OR5B3 NM_001005469.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• Publications: 30 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=0.005467564).
• 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.592A>G	p.Ile198Val	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.592A>G	p.Ile198Val	missense_variant	Exon 2 of 2		NM_001005469.2	ENSP00000493217.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50030 AN: 151902 Hom.: 8318 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.304

GnomAD2 exomes AF: 0.312 AC: 78120 AN: 250662 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: 0.350 AC: 511411 AN: 1460674 Hom.: 91849 Cov.: 35 AF XY: 0.349 AC XY: 253274 AN XY: 726716

African (AFR) AF: 0.326 AC: 10907 AN: 33432

American (AMR) AF: 0.230 AC: 10277 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 8759 AN: 26124

East Asian (EAS) AF: 0.168 AC: 6666 AN: 39694

South Asian (SAS) AF: 0.284 AC: 24530 AN: 86230

European-Finnish (FIN) AF: 0.334 AC: 17826 AN: 53316

Middle Eastern (MID) AF: 0.313 AC: 1801 AN: 5756

European-Non Finnish (NFE) AF: 0.370 AC: 410586 AN: 1111110

Other (OTH) AF: 0.332 AC: 20059 AN: 60356

GnomAD4 genome AF: 0.329 AC: 50045 AN: 152020 Hom.: 8317 Cov.: 32 AF XY: 0.325 AC XY: 24149 AN XY: 74326

African (AFR) AF: 0.325 AC: 13470 AN: 41474

American (AMR) AF: 0.262 AC: 4003 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3468

East Asian (EAS) AF: 0.150 AC: 776 AN: 5164

South Asian (SAS) AF: 0.300 AC: 1446 AN: 4822

European-Finnish (FIN) AF: 0.334 AC: 3527 AN: 10574

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

European-Non Finnish (NFE) AF: 0.362 AC: 24589 AN: 67944

Other (OTH) AF: 0.302 AC: 638 AN: 2112

Alfa AF: 0.349 Hom.: 29734

Bravo AF: 0.321

TwinsUK AF: 0.373 AC: 1384

ALSPAC AF: 0.380 AC: 1463

ESP6500AA AF: 0.328 AC: 1442

ESP6500EA AF: 0.360 AC: 3095

ExAC AF: 0.319 AC: 38683

Asia WGS AF: 0.264 AC: 917 AN: 3478

EpiCase AF: 0.355

EpiControl AF: 0.356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.90	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0060
DANN	Benign	0.19
DEOGEN2	Benign	0.0043	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.062	.;T
MetaRNN	Benign	0.0055	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.32	N;N
PhyloP100		-3.2
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.15	.;N
REVEL	Benign	0.070
Sift	Benign	0.76	.;T
Sift4G	Benign	0.39	.;T
Polyphen		0.0	B;B
Vest4		0.016
MPC		0.027
ClinPred		0.0071	T
GERP RS		-8.1
Varity_R		0.024
gMVP		0.032
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11229410; hg19: chr11-58170291; COSMIC: COSV58676627;