11-5469313-C-T

Variant names:

• chr11-5469313-C-T
• rs366257
• ENST00000292896.3:c.-267+36256G>A

Variant summary

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

The ENST00000292896.3(HBE1):​c.-267+36256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 153,852 control chromosomes in the GnomAD database, including 45,030 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 (44478 hom., cov: 32)
  • Exomes 𝑓: 0.79 (552 hom.)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 4 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]

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]

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 (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51A10P		n.5469313C>T		intragenic_variant
OR51B5	NM_001005567.3	c.-360+36256G>A		intron_variant	Intron 1 of 4		NP_001005567.2
OR51B5	NR_038321.2	n.84+36256G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000239920	ENST00000380259.7	n.*739+121512G>A		intron_variant	Intron 5 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115989 AN: 151938 Hom.: 44440 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.757

GnomAD4 exome AF: 0.786 AC: 1412 AN: 1796 Hom.: 552 Cov.: 0 AF XY: 0.779 AC XY: 760 AN XY: 976

African (AFR) AF: 0.875 AC: 7 AN: 8

American (AMR) AF: 0.733 AC: 129 AN: 176

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 31 AN: 34

East Asian (EAS) AF: 0.786 AC: 11 AN: 14

South Asian (SAS) AF: 0.714 AC: 70 AN: 98

European-Finnish (FIN) AF: 0.700 AC: 28 AN: 40

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.800 AC: 1070 AN: 1338

Other (OTH) AF: 0.738 AC: 62 AN: 84

GnomAD4 genome AF: 0.763 AC: 116084 AN: 152056 Hom.: 44478 Cov.: 32 AF XY: 0.763 AC XY: 56668 AN XY: 74314

African (AFR) AF: 0.700 AC: 29007 AN: 41432

American (AMR) AF: 0.800 AC: 12238 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2531 AN: 3472

East Asian (EAS) AF: 0.669 AC: 3446 AN: 5148

South Asian (SAS) AF: 0.744 AC: 3586 AN: 4818

European-Finnish (FIN) AF: 0.800 AC: 8461 AN: 10576

Middle Eastern (MID) AF: 0.695 AC: 203 AN: 292

European-Non Finnish (NFE) AF: 0.798 AC: 54247 AN: 68004

Other (OTH) AF: 0.757 AC: 1601 AN: 2114

Alfa AF: 0.783 Hom.: 22254

Bravo AF: 0.753

Asia WGS AF: 0.699 AC: 2429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	10
DANN	Benign	0.53
PhyloP100		0.31
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: rs366257; hg19: chr11-5490543;