chr11-5270333-G-GT

Position:

• chr11-5270333-G-GT

Variant summary

Our verdict is Benign. Variant got -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

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]

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBE1	ENST00000292896.3	c.-266-178_-266-177insA		intron_variant		1		ENSP00000292896	P1
HBE1	ENST00000380237.5	c.-266-178_-266-177insA		intron_variant		1		ENSP00000369586	P1
HBG2	ENST00000380252.6	c.-73-15820_-73-15819insA		intron_variant		3		ENSP00000369602
	ENST00000646569.1	n.59-10797_59-10796insA		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.488

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 v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3834466; hg19: chr11-5291563;