ENST00000380259.7:n.*867-4869C>T

Variant names:

• chr11-5260034-G-A
• rs11820733
• ENST00000380259.7:n.*867-4869C>T

Variant summary

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

The ENST00000380259.7(ENSG00000239920):​n.*867-4869C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 152,008 control chromosomes in the GnomAD database, including 2,258 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 0.098 (2258 hom., cov: 32)
• Consequence: ENSG00000239920 ENST00000380259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000239920	ENST00000380259.7	TSL:5	n.*867-4869C>T		intron	N/A	ENSP00000369609.3
	HBG2	ENST00000380252.6	TSL:3	c.-73-5520C>T		intron	N/A	ENSP00000369602.2
	ENSG00000239920	ENST00000643199.1		n.871-1258C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14890 AN: 151890 Hom.: 2255 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0435

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00641

Gnomad OTH AF: 0.0698

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

GnomAD4 genome AF: 0.0982 AC: 14920 AN: 152008 Hom.: 2258 Cov.: 32 AF XY: 0.0944 AC XY: 7018 AN XY: 74318

African (AFR) AF: 0.328 AC: 13568 AN: 41344

American (AMR) AF: 0.0435 AC: 665 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4816

European-Finnish (FIN) AF: 0.00349 AC: 37 AN: 10590

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00641 AC: 436 AN: 67998

Other (OTH) AF: 0.0691 AC: 146 AN: 2114

Alfa AF: 0.0617 Hom.: 144

Bravo AF: 0.116

Asia WGS AF: 0.0210 AC: 74 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.72
PhyloP100		0.23
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: rs11820733; hg19: chr11-5281264;