rs10160820

Positions:

• chr11-5261227-A-C
• chr11-5261227-A-T

Variant summary

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

The ENST00000380252.6(HBG2):​c.-73-6713T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,118 control chromosomes in the GnomAD database, including 5,007 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 0.24 (5007 hom., cov: 32)
• Consequence: HBG2 ENST00000380252.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 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.-73-6713T>G		intron_variant		3
	ENST00000646569.1	n.59-1690T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36284 AN: 152000 Hom.: 5008 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.239 AC: 36283 AN: 152118 Hom.: 5007 Cov.: 32 AF XY: 0.234 AC XY: 17409 AN XY: 74376

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.248

Alfa AF: 0.161 Hom.: 353

Bravo AF: 0.228

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.62

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: rs10160820; hg19: chr11-5282457;