11-5270333-G-GT

Variant names:

• chr11-5270333-G-GT
• rs3834466
• ENST00000292896.3:c.-266-178_-266-177insA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000292896.3(HBE1):​c.-266-178_-266-177insA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (15605 hom., cov: 0)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 21 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]

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBE1	ENST00000292896.3	TSL:1	c.-266-178_-266-177insA		intron	N/A	ENSP00000292896.2	P02100
	HBE1	ENST00000380237.5	TSL:1	c.-266-178_-266-177insA		intron	N/A	ENSP00000369586.1	P02100
	ENSG00000239920	ENST00000380259.7	TSL:5	n.*867-15169_*867-15168insA		intron	N/A	ENSP00000369609.3	A0A2U3TZJ3

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65580 AN: 151920 Hom.: 15593 Cov.: 0

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.432 AC: 65633 AN: 152038 Hom.: 15605 Cov.: 0 AF XY: 0.438 AC XY: 32541 AN XY: 74286

African (AFR) AF: 0.246 AC: 10211 AN: 41476

American (AMR) AF: 0.570 AC: 8711 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2072 AN: 3470

East Asian (EAS) AF: 0.778 AC: 4021 AN: 5170

South Asian (SAS) AF: 0.585 AC: 2820 AN: 4820

European-Finnish (FIN) AF: 0.449 AC: 4734 AN: 10546

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31386 AN: 67968

Other (OTH) AF: 0.488 AC: 1030 AN: 2112

Alfa AF: 0.433 Hom.: 1812

Bravo AF: 0.429

Asia WGS AF: 0.619 AC: 2151 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.080
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3834466; hg19: chr11-5291563;