11-5262916-C-T

Variant names:

• chr11-5262916-C-T
• rs11036507
• ENST00000380259.7:n.*867-7751G>A

Variant summary

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

The ENST00000380259.7(ENSG00000239920):​n.*867-7751G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,110 control chromosomes in the GnomAD database, including 15,611 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 (15611 hom., cov: 33)
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000239920	ENST00000380259.7	n.*867-7751G>A		intron_variant	Intron 6 of 7	5		ENSP00000369609.3
HBG2	ENST00000380252.6	c.-73-8402G>A		intron_variant	Intron 1 of 2	3		ENSP00000369602.2
ENSG00000239920	ENST00000643199.1	n.871-4140G>A		intron_variant	Intron 4 of 6
ENSG00000239920	ENST00000646569.1	n.59-3379G>A		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65838 AN: 151992 Hom.: 15597 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.433 AC: 65900 AN: 152110 Hom.: 15611 Cov.: 33 AF XY: 0.439 AC XY: 32658 AN XY: 74350

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.491

Alfa AF: 0.286 Hom.: 706

Bravo AF: 0.432

Asia WGS AF: 0.593 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.4
DANN	Benign	0.38

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: rs11036507; hg19: chr11-5284146;