rs3759071

Variant names:

• chr11-5270302-G-A
• rs3759071
• ENST00000292896.3:c.-266-146C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5270302-G-A
• chr11-5270302-G-T

Variant summary

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

The ENST00000292896.3(HBE1):​c.-266-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 167,790 control chromosomes in the GnomAD database, including 19,120 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 0.47 (17217 hom., cov: 32)
  • Exomes 𝑓: 0.46 (1903 hom.)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.913
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 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.*867-15137C>T		intron_variant	Intron 6 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70727 AN: 151866 Hom.: 17202 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.465 AC: 7349 AN: 15806 Hom.: 1903 AF XY: 0.473 AC XY: 3800 AN XY: 8030

African (AFR) AF: 0.346 AC: 153 AN: 442

American (AMR) AF: 0.578 AC: 901 AN: 1560

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 235 AN: 400

East Asian (EAS) AF: 0.727 AC: 416 AN: 572

South Asian (SAS) AF: 0.567 AC: 475 AN: 838

European-Finnish (FIN) AF: 0.430 AC: 265 AN: 616

Middle Eastern (MID) AF: 0.696 AC: 32 AN: 46

European-Non Finnish (NFE) AF: 0.427 AC: 4445 AN: 10404

Other (OTH) AF: 0.460 AC: 427 AN: 928

GnomAD4 genome AF: 0.466 AC: 70789 AN: 151984 Hom.: 17217 Cov.: 32 AF XY: 0.471 AC XY: 35003 AN XY: 74260

African (AFR) AF: 0.366 AC: 15140 AN: 41404

American (AMR) AF: 0.582 AC: 8886 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2063 AN: 3470

East Asian (EAS) AF: 0.777 AC: 4025 AN: 5178

South Asian (SAS) AF: 0.583 AC: 2807 AN: 4818

European-Finnish (FIN) AF: 0.451 AC: 4748 AN: 10538

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31396 AN: 67982

Other (OTH) AF: 0.509 AC: 1073 AN: 2108

Alfa AF: 0.474 Hom.: 22945

Bravo AF: 0.473

Asia WGS AF: 0.624 AC: 2170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.0
DANN	Benign	0.40
PhyloP100		0.91
PromoterAI		-0.0062	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3759071; hg19: chr11-5291532;