11-5253037-C-T

Variant names:

• chr11-5253037-C-T
• rs2236794
• ENST00000642908.1:c.315+1255G>A

Variant summary

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

The ENST00000642908.1(ENSG00000284931):​c.315+1255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,970 control chromosomes in the GnomAD database, including 15,562 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 (15562 hom., cov: 33)
• Consequence: ENSG00000284931 ENST00000642908.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

Genes affected

ENSG00000284931 (HGNC:):

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBG2	NM_000184.3	c.*240G>A		downstream_gene_variant		ENST00000336906.6	NP_000175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284931	ENST00000642908.1	c.315+1255G>A		intron_variant	Intron 2 of 2			ENSP00000495346.1
ENSG00000284931	ENST00000647543.1	c.378+306G>A		intron_variant	Intron 3 of 3			ENSP00000496470.1
HBG2	ENST00000336906.6	c.*240G>A		downstream_gene_variant		1	NM_000184.3	ENSP00000338082.4
HBG2	ENST00000380252.6	c.*240G>A		downstream_gene_variant		3		ENSP00000369602.2

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65024 AN: 151852 Hom.: 15549 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.428 AC: 65074 AN: 151970 Hom.: 15562 Cov.: 33 AF XY: 0.435 AC XY: 32280 AN XY: 74238

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.490

Alfa AF: 0.455 Hom.: 5765

Bravo AF: 0.425

Asia WGS AF: 0.597 AC: 2077 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2236794; hg19: chr11-5274267;