11-5261278-T-C

Variant names:

• chr11-5261278-T-C
• rs7480802
• ENST00000380259.7:n.*867-6113A>G

Variant summary

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

The ENST00000380259.7(ENSG00000239920):​n.*867-6113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,926 control chromosomes in the GnomAD database, including 21,922 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 (21922 hom., cov: 32)
• Consequence: ENSG00000239920 ENST00000380259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 1 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000380259.7. 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
	ENSG00000239920	ENST00000380259.7	TSL:5	n.*867-6113A>G		intron	N/A	ENSP00000369609.3	A0A2U3TZJ3
	HBG2	ENST00000380252.6	TSL:3	c.-73-6764A>G		intron	N/A	ENSP00000369602.2	E9PBW4
	ENSG00000239920	ENST00000643199.1		n.871-2502A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80651 AN: 151808 Hom.: 21895 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.531 AC: 80738 AN: 151926 Hom.: 21922 Cov.: 32 AF XY: 0.534 AC XY: 39602 AN XY: 74228

African (AFR) AF: 0.581 AC: 24090 AN: 41440

American (AMR) AF: 0.618 AC: 9439 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2129 AN: 3470

East Asian (EAS) AF: 0.774 AC: 4005 AN: 5172

South Asian (SAS) AF: 0.540 AC: 2595 AN: 4804

European-Finnish (FIN) AF: 0.452 AC: 4765 AN: 10540

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31880 AN: 67916

Other (OTH) AF: 0.560 AC: 1181 AN: 2110

Alfa AF: 0.360 Hom.: 916

Bravo AF: 0.547

Asia WGS AF: 0.613 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.1
DANN	Benign	0.83
PhyloP100		-1.1
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: rs7480802; hg19: chr11-5282508;