11-5295501-G-C

Variant names:

• chr11-5295501-G-C
• rs7933082
• ENST00000292896.3:c.-266-25345C>G

Variant summary

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

The ENST00000292896.3(HBE1):​c.-266-25345C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 149,280 control chromosomes in the GnomAD database, including 21,225 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 0.54 (21225 hom., cov: 30)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 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.-266-25345C>G		intron	N/A	ENSP00000292896.2	P02100
	HBE1	ENST00000380237.5	TSL:1	c.-309-13550C>G		intron	N/A	ENSP00000369586.1	P02100
	ENSG00000239920	ENST00000380259.7	TSL:5	n.*867-40336C>G		intron	N/A	ENSP00000369609.3	A0A2U3TZJ3

Frequencies

GnomAD3 genomes AF: 0.535 AC: 79870 AN: 149160 Hom.: 21213 Cov.: 30

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.600

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.535 AC: 79923 AN: 149280 Hom.: 21225 Cov.: 30 AF XY: 0.540 AC XY: 39454 AN XY: 73064

African (AFR) AF: 0.554 AC: 22484 AN: 40600

American (AMR) AF: 0.596 AC: 8931 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1765 AN: 3416

East Asian (EAS) AF: 0.786 AC: 3996 AN: 5086

South Asian (SAS) AF: 0.573 AC: 2730 AN: 4762

European-Finnish (FIN) AF: 0.522 AC: 5449 AN: 10440

Middle Eastern (MID) AF: 0.590 AC: 171 AN: 290

European-Non Finnish (NFE) AF: 0.492 AC: 32808 AN: 66718

Other (OTH) AF: 0.563 AC: 1168 AN: 2074

Alfa AF: 0.209 Hom.: 253

Bravo AF: 0.544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.44
PhyloP100		0.65
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: rs7933082; hg19: chr11-5316731;