11-5351626-A-G

Position:

• chr11-5351626-A-G

Variant summary

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

The NM_001004750.1(OR51B6):​c.119A>G​(p.Asn40Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,613,622 control chromosomes in the GnomAD database, including 32,242 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 0.19 (3048 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29194 hom.)
• Consequence: OR51B6 NM_001004750.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.21

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=0.001967311).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR51B6	NM_001004750.1	c.119A>G	p.Asn40Ser	missense_variant	1/1	ENST00000380219.1	NP_001004750.1
OR51B5	NM_001005567.3	c.-359-4716T>C		intron_variant			NP_001005567.2
OR51B5	NR_038321.2	n.85-4716T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR51B6	ENST00000380219.1	c.119A>G	p.Asn40Ser	missense_variant	1/1	6	NM_001004750.1	ENSP00000369568.1
ENSG00000239920	ENST00000380259.7	n.*740-5727T>C		intron_variant		5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29513 AN: 151948 Hom.: 3043 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.185

GnomAD3 exomes AF: 0.164 AC: 41156 AN: 251282 Hom.: 3892 AF XY: 0.164 AC XY: 22270 AN XY: 135810

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.00941

Gnomad SAS exome AF: 0.125

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.194 AC: 283740 AN: 1461556 Hom.: 29194 Cov.: 35 AF XY: 0.192 AC XY: 139661 AN XY: 727112

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.00894

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.194 AC: 29541 AN: 152066 Hom.: 3048 Cov.: 32 AF XY: 0.191 AC XY: 14210 AN XY: 74338

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0127

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.183

Alfa AF: 0.197 Hom.: 8058

Bravo AF: 0.191

TwinsUK AF: 0.215 AC: 797

ALSPAC AF: 0.204 AC: 786

ESP6500AA AF: 0.197 AC: 869

ESP6500EA AF: 0.212 AC: 1824

ExAC AF: 0.167 AC: 20224

Asia WGS AF: 0.112 AC: 388 AN: 3478

EpiCase AF: 0.202

EpiControl AF: 0.201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.5	M
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.49	P
Vest4		0.27
MPC		0.010
ClinPred		0.095	T
GERP RS		4.0
Varity_R		0.80
gMVP		0.59

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: rs4910756; hg19: chr11-5372856;