11-5256061-C-T

Position:

• chr11-5256061-C-T

Variant summary

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

The ENST00000380259.7(ENSG00000239920):​n.*867-896G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,018 control chromosomes in the GnomAD database, including 5,113 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 0.25 (5113 hom., cov: 32)
• Consequence: ENSG00000239920 ENST00000380259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

ENSG00000239920 (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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.5256061C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000239920	ENST00000380259.7	n.*867-896G>A		intron_variant		5		ENSP00000369609.3
HBG2	ENST00000380252.6	c.-73-1547G>A		intron_variant		3		ENSP00000369602.2
ENSG00000239920	ENST00000643199.1	n.1053-896G>A		intron_variant
ENSG00000239920	ENST00000646569.1	n.280-896G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37391 AN: 151900 Hom.: 5116 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.246 AC: 37397 AN: 152018 Hom.: 5113 Cov.: 32 AF XY: 0.241 AC XY: 17916 AN XY: 74306

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.253

Alfa AF: 0.284 Hom.: 827

Bravo AF: 0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.45

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: rs2855121; hg19: chr11-5277291;