chr11-5288158-A-C

Variant names:

• chr11-5288158-A-C
• rs11826674
• ENST00000292896.3:c.-266-18002T>G

Variant summary

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

The ENST00000292896.3(HBE1):​c.-266-18002T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 152,306 control chromosomes in the GnomAD database, including 413 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 0.045 (413 hom., cov: 32)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 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.*867-32993T>G		intron_variant	Intron 6 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6900 AN: 152188 Hom.: 408 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0218

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00794

Gnomad OTH AF: 0.0372

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

GnomAD4 genome AF: 0.0455 AC: 6924 AN: 152306 Hom.: 413 Cov.: 32 AF XY: 0.0439 AC XY: 3268 AN XY: 74480

African (AFR) AF: 0.140 AC: 5825 AN: 41552

American (AMR) AF: 0.0218 AC: 333 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4828

European-Finnish (FIN) AF: 0.00612 AC: 65 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00794 AC: 540 AN: 68028

Other (OTH) AF: 0.0369 AC: 78 AN: 2116

Alfa AF: 0.0312 Hom.: 37

Bravo AF: 0.0497

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.91
DANN	Benign	0.82
PhyloP100		-0.39
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: rs11826674; hg19: chr11-5309388;