rs5006884

Positions:

• chr11-5352021-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004750.1(OR51B6):​c.514C>T​(p.Leu172Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,603,842 control chromosomes in the GnomAD database, including 54,593 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.26 (5515 hom., cov: 32)
  • Exomes 𝑓: 0.25 (49078 hom.)
• Consequence: OR51B6 NM_001004750.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

Genes affected

OR51B6 (HGNC:19600): (olfactory receptor family 51 subfamily B member 6) 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]

HBE1 (HGNC:4830): (hemoglobin subunit epsilon 1) The epsilon globin gene (HBE) is normally expressed in the embryonic yolk sac: two epsilon chains together with two zeta chains (an alpha-like globin) constitute the embryonic hemoglobin Hb Gower I; two epsilon chains together with two alpha chains form the embryonic Hb Gower II. Both of these embryonic hemoglobins are normally supplanted by fetal, and later, adult hemoglobin. The five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon - G-gamma - A-gamma - delta - beta-3' [provided by RefSeq, Jul 2008]

ENSG00000239920 (HGNC:):

OR51B5 (HGNC:19599): (olfactory receptor family 51 subfamily B member 5) 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]

HBG2 (HGNC:4832): (hemoglobin subunit gamma 2) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'- epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0068277717).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR51B6	NM_001004750.1	c.514C>T	p.Leu172Phe	missense_variant	1/1	ENST00000380219.1	NP_001004750.1
OR51B5	NM_001005567.3	c.-359-5111G>A		intron_variant			NP_001005567.2
OR51B5	NR_038321.2	n.85-5111G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR51B6	ENST00000380219.1	c.514C>T	p.Leu172Phe	missense_variant	1/1	6	NM_001004750.1	ENSP00000369568.1
ENSG00000239920	ENST00000380259.7	n.*740-6122G>A		intron_variant		5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40104 AN: 151854 Hom.: 5505 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.261

GnomAD3 exomes AF: 0.237 AC: 59344 AN: 250830 Hom.: 7604 AF XY: 0.236 AC XY: 31951 AN XY: 135534

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.0611

Gnomad SAS exome AF: 0.229

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.237

GnomAD4 exome AF: 0.254 AC: 368522 AN: 1451870 Hom.: 49078 Cov.: 49 AF XY: 0.253 AC XY: 182702 AN XY: 722682

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0551

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.264 AC: 40142 AN: 151972 Hom.: 5515 Cov.: 32 AF XY: 0.261 AC XY: 19420 AN XY: 74274

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.259

Alfa AF: 0.257 Hom.: 11775

Bravo AF: 0.263

TwinsUK AF: 0.274 AC: 1017

ALSPAC AF: 0.251 AC: 966

ESP6500AA AF: 0.292 AC: 1285

ESP6500EA AF: 0.264 AC: 2270

ExAC AF: 0.239 AC: 28970

Asia WGS AF: 0.212 AC: 739 AN: 3478

EpiCase AF: 0.258

EpiControl AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.080
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0068	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.5	H
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.092
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.14
MPC		0.013
ClinPred		0.049	T
GERP RS		3.3
Varity_R		0.79
gMVP		0.029

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: rs5006884; hg19: chr11-5373251;