ENST00000380259.7:n.*867-6062T>G

Variant names:

• chr11-5261227-A-C
• rs10160820
• ENST00000380259.7:n.*867-6062T>G

Variant summary

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

The ENST00000380259.7(ENSG00000239920):​n.*867-6062T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,118 control chromosomes in the GnomAD database, including 5,007 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 0.24 (5007 hom., cov: 32)
• Consequence: ENSG00000239920 ENST00000380259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 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.*867-6062T>G		intron_variant	Intron 6 of 7	5		ENSP00000369609.3
HBG2	ENST00000380252.6	c.-73-6713T>G		intron_variant	Intron 1 of 2	3		ENSP00000369602.2
ENSG00000239920	ENST00000643199.1	n.871-2451T>G		intron_variant	Intron 4 of 6
ENSG00000239920	ENST00000646569.1	n.59-1690T>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36284 AN: 152000 Hom.: 5008 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.239 AC: 36283 AN: 152118 Hom.: 5007 Cov.: 32 AF XY: 0.234 AC XY: 17409 AN XY: 74376

African (AFR) AF: 0.126 AC: 5219 AN: 41542

American (AMR) AF: 0.211 AC: 3215 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3468

East Asian (EAS) AF: 0.120 AC: 622 AN: 5178

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4810

European-Finnish (FIN) AF: 0.227 AC: 2400 AN: 10588

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21906 AN: 67948

Other (OTH) AF: 0.248 AC: 524 AN: 2110

Alfa AF: 0.0590 Hom.: 371

Bravo AF: 0.228

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.62
PhyloP100		0.21
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: rs10160820; hg19: chr11-5282457;