rs10837771

Variant names:

• chr11-5301507-A-G
• rs10837771
• NM_033179.2:c.440T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-5301507-A-G
• chr11-5301507-A-T

Variant summary

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

The NM_033179.2(OR51B4):​c.440T>C​(p.Met147Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,613,876 control chromosomes in the GnomAD database, including 151,635 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 0.37 (12419 hom., cov: 31)
  • Exomes 𝑓: 0.43 (139216 hom.)
• Consequence: OR51B4 NM_033179.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764
• Publications: 30 publications found

Genes affected

OR51B4 (HGNC:14708): (olfactory receptor family 51 subfamily B member 4) 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:):

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]

HBG2 Gene-Disease associations (from GenCC):

• hemoglobinopathy Toms River

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary persistence of fetal hemoglobin-sickle cell disease syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• cyanosis, transient neonatal

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=2.029782E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51B4	NM_033179.2	c.440T>C	p.Met147Thr	missense_variant	Exon 1 of 1	ENST00000380224.2	NP_149419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR51B4	ENST00000380224.2	c.440T>C	p.Met147Thr	missense_variant	Exon 1 of 1	6	NM_033179.2	ENSP00000369573.1
ENSG00000239920	ENST00000380259.7	n.*866+44266T>C		intron_variant	Intron 6 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56977 AN: 151986 Hom.: 12421 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.437

GnomAD2 exomes AF: 0.460 AC: 115600 AN: 251410 AF XY: 0.471

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.463

Gnomad ASJ exome AF: 0.465

Gnomad EAS exome AF: 0.754

Gnomad FIN exome AF: 0.436

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.429 AC: 627198 AN: 1461774 Hom.: 139216 Cov.: 60 AF XY: 0.433 AC XY: 314994 AN XY: 727194

African (AFR) AF: 0.153 AC: 5136 AN: 33480

American (AMR) AF: 0.465 AC: 20809 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 12098 AN: 26134

East Asian (EAS) AF: 0.713 AC: 28308 AN: 39700

South Asian (SAS) AF: 0.537 AC: 46319 AN: 86256

European-Finnish (FIN) AF: 0.436 AC: 23296 AN: 53412

Middle Eastern (MID) AF: 0.582 AC: 3358 AN: 5768

European-Non Finnish (NFE) AF: 0.415 AC: 461073 AN: 1111924

Other (OTH) AF: 0.444 AC: 26801 AN: 60390

GnomAD4 genome AF: 0.375 AC: 56985 AN: 152102 Hom.: 12419 Cov.: 31 AF XY: 0.382 AC XY: 28425 AN XY: 74362

African (AFR) AF: 0.161 AC: 6677 AN: 41512

American (AMR) AF: 0.474 AC: 7246 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1569 AN: 3468

East Asian (EAS) AF: 0.751 AC: 3876 AN: 5162

South Asian (SAS) AF: 0.539 AC: 2598 AN: 4820

European-Finnish (FIN) AF: 0.445 AC: 4702 AN: 10572

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28819 AN: 67972

Other (OTH) AF: 0.438 AC: 926 AN: 2112

Alfa AF: 0.415 Hom.: 55963

Bravo AF: 0.365

TwinsUK AF: 0.416 AC: 1542

ALSPAC AF: 0.408 AC: 1571

ESP6500AA AF: 0.166 AC: 730

ESP6500EA AF: 0.436 AC: 3745

ExAC AF: 0.456 AC: 55366

Asia WGS AF: 0.570 AC: 1983 AN: 3478

EpiCase AF: 0.445

EpiControl AF: 0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.4
DANN	Benign	0.55
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.016	T
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.15	N
PhyloP100		0.76
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.016
Sift	Benign	0.26	T
Sift4G	Benign	0.34	T
Polyphen		0.016	B
Vest4		0.022
MPC		0.0082
ClinPred		0.010	T
GERP RS		2.6
PromoterAI		-0.018	Neutral
Varity_R		0.11
gMVP		0.11
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: rs10837771; hg19: chr11-5322737; COSMIC: COSV66516920; COSMIC: COSV66516920;