11-5270398-C-G

Variant names:

• chr11-5270398-C-G
• rs3759070
• ENST00000292896.3:c.-266-242G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000292896.3(HBE1):​c.-266-242G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,110 control chromosomes in the GnomAD database, including 8,191 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 0.32 (8191 hom., cov: 32)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.542

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000239920	ENST00000380259.7	n.*867-15233G>C		intron_variant	Intron 6 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48646 AN: 151992 Hom.: 8186 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.320 AC: 48689 AN: 152110 Hom.: 8191 Cov.: 32 AF XY: 0.313 AC XY: 23260 AN XY: 74354

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.318

Alfa AF: 0.227 Hom.: 515

Bravo AF: 0.316

Asia WGS AF: 0.229 AC: 796 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	0.94
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs3759070; hg19: chr11-5291628;