rs449937

Variant names:

• chr11-5469115-G-A
• rs449937
• ENST00000292896.3:c.-267+36454C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5469115-G-A
• chr11-5469115-G-T

Variant summary

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

The NM_001005567.3(OR51B5):​c.-360+36454C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 224,600 control chromosomes in the GnomAD database, including 65,424 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.

• Frequency:
  • Genomes: 𝑓 0.76 (43542 hom., cov: 31)
  • Exomes 𝑓: 0.77 (21882 hom.)
• Consequence: OR51B5 NM_001005567.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• Publications: 7 publications found

Genes affected

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]

OR51A10P (HGNC:15185): (olfactory receptor family 51 subfamily A member 10 pseudogene) 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 (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005567.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR51B5	NM_001005567.3		c.-360+36454C>T		intron	N/A	NP_001005567.2	Q9H339
	OR51B5	NR_038321.2		n.84+36454C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBE1	ENST00000292896.3	TSL:1	c.-267+36454C>T		intron	N/A	ENSP00000292896.2	P02100
	HBE1	ENST00000380237.5	TSL:1	c.-310+36454C>T		intron	N/A	ENSP00000369586.1	P02100
	ENSG00000239920	ENST00000380259.7	TSL:5	n.*739+121710C>T		intron	N/A	ENSP00000369609.3	A0A2U3TZJ3

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114806 AN: 151924 Hom.: 43501 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.751

GnomAD4 exome AF: 0.771 AC: 55953 AN: 72558 Hom.: 21882 Cov.: 0 AF XY: 0.768 AC XY: 29423 AN XY: 38336

African (AFR) AF: 0.707 AC: 1216 AN: 1720

American (AMR) AF: 0.773 AC: 2374 AN: 3070

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 1258 AN: 1714

East Asian (EAS) AF: 0.672 AC: 1497 AN: 2228

South Asian (SAS) AF: 0.733 AC: 8286 AN: 11304

European-Finnish (FIN) AF: 0.815 AC: 3288 AN: 4034

Middle Eastern (MID) AF: 0.786 AC: 352 AN: 448

European-Non Finnish (NFE) AF: 0.785 AC: 34471 AN: 43890

Other (OTH) AF: 0.774 AC: 3211 AN: 4150

GnomAD4 genome AF: 0.756 AC: 114904 AN: 152042 Hom.: 43542 Cov.: 31 AF XY: 0.755 AC XY: 56123 AN XY: 74318

African (AFR) AF: 0.698 AC: 28926 AN: 41458

American (AMR) AF: 0.793 AC: 12123 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2517 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3444 AN: 5154

South Asian (SAS) AF: 0.742 AC: 3569 AN: 4808

European-Finnish (FIN) AF: 0.796 AC: 8419 AN: 10580

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53350 AN: 67978

Other (OTH) AF: 0.752 AC: 1587 AN: 2110

Alfa AF: 0.771 Hom.: 137119

Bravo AF: 0.746

Asia WGS AF: 0.697 AC: 2425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		3.2
Mutation Taster		=97/3	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: rs449937; hg19: chr11-5490345;