11-5255848-A-T

Position:

• chr11-5255848-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000380252.6(HBG2):​c.-73-1334T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,992 control chromosomes in the GnomAD database, including 15,701 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 0.43 (15701 hom., cov: 33)
• Consequence: HBG2 ENST00000380252.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBG2	ENST00000380252.6	c.-73-1334T>A		intron_variant		3
	ENST00000646569.1	n.280-683T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65863 AN: 151874 Hom.: 15690 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.434 AC: 65917 AN: 151992 Hom.: 15701 Cov.: 33 AF XY: 0.440 AC XY: 32679 AN XY: 74292

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.493

Alfa AF: 0.435 Hom.: 1862

Bravo AF: 0.431

Asia WGS AF: 0.596 AC: 2073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs2855123; hg19: chr11-5277078;