rs7130110

Variant names:

• chr11-5274874-G-C
• rs7130110
• ENST00000292896.3:c.-266-4718C>G

Variant summary

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

The ENST00000292896.3(HBE1):​c.-266-4718C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,994 control chromosomes in the GnomAD database, including 37,865 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 0.68 (37865 hom., cov: 32)
• Consequence: HBE1 ENST00000292896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700
• Publications: 5 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 = 0.905 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.*867-19709C>G		intron_variant	Intron 6 of 7	5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104031 AN: 151876 Hom.: 37851 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.685 AC: 104075 AN: 151994 Hom.: 37865 Cov.: 32 AF XY: 0.690 AC XY: 51263 AN XY: 74276

African (AFR) AF: 0.415 AC: 17205 AN: 41414

American (AMR) AF: 0.824 AC: 12570 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2688 AN: 3468

East Asian (EAS) AF: 0.927 AC: 4785 AN: 5164

South Asian (SAS) AF: 0.808 AC: 3891 AN: 4818

European-Finnish (FIN) AF: 0.737 AC: 7789 AN: 10566

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52703 AN: 67990

Other (OTH) AF: 0.752 AC: 1587 AN: 2110

Alfa AF: 0.717 Hom.: 5017

Bravo AF: 0.675

Asia WGS AF: 0.833 AC: 2895 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	0.34
DANN	Benign	0.47
PhyloP100		-0.70
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: rs7130110; hg19: chr11-5296104;