rs2156918

Variant names:

• chr11-5275662-G-A
• rs2156918
• ENST00000292896.3:c.-266-5506C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5275662-G-A
• chr11-5275662-G-C
• chr11-5275662-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000292896.3(HBE1):​c.-266-5506C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00045 (0 hom., cov: 32)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.*867-20497C>T		intron_variant	Intron 6 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.000454 AC: 69 AN: 151992 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.000960

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

GnomAD4 genome AF: 0.000454 AC: 69 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.000565 AC XY: 42 AN XY: 74352

African (AFR) AF: 0.000145 AC: 6 AN: 41454

American (AMR) AF: 0.000785 AC: 12 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000624 AC: 3 AN: 4806

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10588

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68022

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.000506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.93
PhyloP100		-1.7

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: rs2156918; hg19: chr11-5296892;