chr11-5254177-T-C

Position:

• chr11-5254177-T-C

Variant summary

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

The ENST00000336906.6(HBG2):​c.315+115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,087,456 control chromosomes in the GnomAD database, including 90,851 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 0.44 (15832 hom., cov: 33)
  • Exomes 𝑓: 0.36 (75019 hom.)
• Consequence: HBG2 ENST00000336906.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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	Protein	UniProt
HBG2	NM_000184.3	c.315+115A>G		intron_variant		ENST00000336906.6	NP_000175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBG2	ENST00000336906.6	c.315+115A>G		intron_variant		1	NM_000184.3	ENSP00000338082	P1
HBG2	ENST00000380252.6	c.150+115A>G		intron_variant		3		ENSP00000369602
HBG2	ENST00000444587.1	c.*184+115A>G		intron_variant		2		ENSP00000488218

Frequencies

GnomAD3 genomes AF: 0.438 AC: 65471 AN: 149366 Hom.: 15818 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.357 AC: 334771 AN: 937978 Hom.: 75019 AF XY: 0.369 AC XY: 177264 AN XY: 479898

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.707

Gnomad4 SAS exome AF: 0.494

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.438 AC: 65523 AN: 149478 Hom.: 15832 Cov.: 33 AF XY: 0.445 AC XY: 32498 AN XY: 73076

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.498

Alfa AF: 0.435 Hom.: 1631

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.55

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: rs2070973; hg19: chr11-5275407;