11-5266060-G-A

Variant names:

• chr11-5266060-G-A
• rs4910740
• ENST00000380259.7:n.*867-10895C>T

Variant summary

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

The ENST00000380259.7(ENSG00000239920):​n.*867-10895C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,874 control chromosomes in the GnomAD database, including 17,066 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 0.46 (17066 hom., cov: 32)
• Consequence: ENSG00000239920 ENST00000380259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 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.*867-10895C>T		intron_variant	Intron 6 of 7	5		ENSP00000369609.3
HBG2	ENST00000380252.6	c.-73-11546C>T		intron_variant	Intron 1 of 2	3		ENSP00000369602.2
ENSG00000239920	ENST00000643199.1	n.870+2310C>T		intron_variant	Intron 4 of 6
ENSG00000239920	ENST00000646569.1	n.59-6523C>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70481 AN: 151754 Hom.: 17045 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.465 AC: 70567 AN: 151874 Hom.: 17066 Cov.: 32 AF XY: 0.469 AC XY: 34823 AN XY: 74234

African (AFR) AF: 0.366 AC: 15166 AN: 41458

American (AMR) AF: 0.589 AC: 8986 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2072 AN: 3458

East Asian (EAS) AF: 0.775 AC: 3995 AN: 5158

South Asian (SAS) AF: 0.540 AC: 2608 AN: 4826

European-Finnish (FIN) AF: 0.449 AC: 4734 AN: 10540

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

European-Non Finnish (NFE) AF: 0.461 AC: 31274 AN: 67870

Other (OTH) AF: 0.512 AC: 1078 AN: 2106

Alfa AF: 0.471 Hom.: 20388

Bravo AF: 0.470

Asia WGS AF: 0.602 AC: 2088 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.2
DANN	Benign	0.52
PhyloP100		-0.30
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: rs4910740; hg19: chr11-5287290;