rs10837707

chr11-5265578-T-C

Variant summary

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

The ENST00000380252.6(HBG2):c.-73-11064A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,818 control chromosomes in the GnomAD database, including 15,277 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 (15277 hom., cov: 32)
• Consequence: HBG2 ENST00000380252.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 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.-73-11064A>G		intron_variant		3
	ENST00000646569.1	n.59-6041A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64702 AN: 151700 Hom.: 15265 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.427 AC: 64754 AN: 151818 Hom.: 15277 Cov.: 32 AF XY: 0.433 AC XY: 32101 AN XY: 74206

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.489

Alfa AF: 0.430 Hom.: 1820

Bravo AF: 0.424

Asia WGS AF: 0.592 AC: 2059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	3.5
Dann	Benign	0.94

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: rs10837707; hg19: chr11-5286808;