11-5256006-C-T

Variant names:

• chr11-5256006-C-T
• rs2855122
• ENST00000380259.7:n.*867-841G>A

Variant summary

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

The ENST00000380259.7(ENSG00000239920):​n.*867-841G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,840 control chromosomes in the GnomAD database, including 22,091 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 0.53 (22091 hom., cov: 31)
• Consequence: ENSG00000239920 ENST00000380259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 14 publications found

Genes affected

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 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.*867-841G>A		intron_variant	Intron 6 of 7	5		ENSP00000369609.3
HBG2	ENST00000380252.6	c.-73-1492G>A		intron_variant	Intron 1 of 2	3		ENSP00000369602.2
ENSG00000239920	ENST00000643199.1	n.1053-841G>A		intron_variant	Intron 6 of 6
ENSG00000239920	ENST00000646569.1	n.280-841G>A		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80960 AN: 151722 Hom.: 22063 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.534 AC: 81047 AN: 151840 Hom.: 22091 Cov.: 31 AF XY: 0.536 AC XY: 39784 AN XY: 74188

African (AFR) AF: 0.582 AC: 24094 AN: 41416

American (AMR) AF: 0.621 AC: 9470 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2197 AN: 3464

East Asian (EAS) AF: 0.775 AC: 3995 AN: 5152

South Asian (SAS) AF: 0.549 AC: 2633 AN: 4798

European-Finnish (FIN) AF: 0.465 AC: 4886 AN: 10512

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31928 AN: 67932

Other (OTH) AF: 0.564 AC: 1191 AN: 2110

Alfa AF: 0.488 Hom.: 14553

Bravo AF: 0.548

Asia WGS AF: 0.616 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.39
PhyloP100		-0.32
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: rs2855122; hg19: chr11-5277236;