ENST00000380259.7:n.*867-896G>A

Variant names:

• chr11-5256061-C-T
• rs2855121
• ENST00000380259.7:n.*867-896G>A

Variant summary

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

The ENST00000380259.7(ENSG00000239920):​n.*867-896G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,018 control chromosomes in the GnomAD database, including 5,113 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 0.25 (5113 hom., cov: 32)
• Consequence: ENSG00000239920 ENST00000380259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 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.*867-896G>A		intron	N/A	ENSP00000369609.3	A0A2U3TZJ3
	HBG2	ENST00000380252.6	TSL:3	c.-73-1547G>A		intron	N/A	ENSP00000369602.2	E9PBW4
	ENSG00000239920	ENST00000643199.1		n.1053-896G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37391 AN: 151900 Hom.: 5116 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.246 AC: 37397 AN: 152018 Hom.: 5113 Cov.: 32 AF XY: 0.241 AC XY: 17916 AN XY: 74306

African (AFR) AF: 0.160 AC: 6653 AN: 41472

American (AMR) AF: 0.210 AC: 3210 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 699 AN: 3468

East Asian (EAS) AF: 0.120 AC: 621 AN: 5162

South Asian (SAS) AF: 0.274 AC: 1316 AN: 4804

European-Finnish (FIN) AF: 0.216 AC: 2282 AN: 10568

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21808 AN: 67962

Other (OTH) AF: 0.253 AC: 535 AN: 2114

Alfa AF: 0.284 Hom.: 827

Bravo AF: 0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.45
PhyloP100		-1.4
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: rs2855121; hg19: chr11-5277291;