11-5262949-C-T

Position:

• chr11-5262949-C-T

Variant summary

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

The ENST00000380259.7(ENSG00000239920):​n.*867-7784G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,106 control chromosomes in the GnomAD database, including 6,801 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 0.29 (6801 hom., cov: 32)
• Consequence: ENSG00000239920 ENST00000380259.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.5262949C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000239920	ENST00000380259.7	n.*867-7784G>A		intron_variant		5		ENSP00000369609.3
HBG2	ENST00000380252.6	c.-73-8435G>A		intron_variant		3		ENSP00000369602.2
ENSG00000239920	ENST00000643199.1	n.871-4173G>A		intron_variant
ENSG00000239920	ENST00000646569.1	n.59-3412G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44267 AN: 151988 Hom.: 6796 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.291 AC: 44298 AN: 152106 Hom.: 6801 Cov.: 32 AF XY: 0.285 AC XY: 21168 AN XY: 74348

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.289

Alfa AF: 0.298 Hom.: 857

Bravo AF: 0.290

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.52

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: rs10160747; hg19: chr11-5284179;