chr11-5302158-G-A

Variant names:

• chr11-5302158-G-A
• rs10837774
• ENST00000292896.3:c.-266-32002C>T

Variant summary

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

The ENST00000292896.3(HBE1):​c.-266-32002C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,022 control chromosomes in the GnomAD database, including 4,256 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 0.23 (4256 hom., cov: 32)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855
• 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:):

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000292896.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR51B4	NM_033179.2	MANE Select	c.-212C>T		upstream_gene	N/A	NP_149419.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBE1	ENST00000292896.3	TSL:1	c.-266-32002C>T		intron	N/A	ENSP00000292896.2
	HBE1	ENST00000380237.5	TSL:1	c.-309-20207C>T		intron	N/A	ENSP00000369586.1
	ENSG00000239920	ENST00000380259.7	TSL:5	n.*866+43615C>T		intron	N/A	ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34187 AN: 151904 Hom.: 4253 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 34211 AN: 152022 Hom.: 4256 Cov.: 32 AF XY: 0.221 AC XY: 16409 AN XY: 74306

African (AFR) AF: 0.151 AC: 6250 AN: 41484

American (AMR) AF: 0.252 AC: 3847 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3466

East Asian (EAS) AF: 0.143 AC: 740 AN: 5178

South Asian (SAS) AF: 0.226 AC: 1087 AN: 4816

European-Finnish (FIN) AF: 0.182 AC: 1924 AN: 10554

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.276 AC: 18773 AN: 67930

Other (OTH) AF: 0.236 AC: 497 AN: 2110

Alfa AF: 0.215 Hom.: 1404

Bravo AF: 0.230

Asia WGS AF: 0.214 AC: 744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.61
DANN	Benign	0.33
PhyloP100		-0.85
PromoterAI		0.0032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10837774; hg19: chr11-5323388;