chr11-5261664-C-A

Position:

• chr11-5261664-C-A

Variant summary

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

The ENST00000380252.6(HBG2):​c.-73-7150G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,018 control chromosomes in the GnomAD database, including 51,644 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 0.82 (51644 hom., cov: 31)
• Consequence: HBG2 ENST00000380252.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 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.-73-7150G>T		intron_variant		3
	ENST00000646569.1	n.59-2127G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124911 AN: 151900 Hom.: 51587 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.822 AC: 125030 AN: 152018 Hom.: 51644 Cov.: 31 AF XY: 0.818 AC XY: 60781 AN XY: 74296

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.849

Alfa AF: 0.804 Hom.: 6115

Bravo AF: 0.837

Asia WGS AF: 0.859 AC: 2990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.81
DANN	Benign	0.30

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: rs10160678; hg19: chr11-5282894;