ENST00000643122.1:c.-28-4036C>G

Variant names:

• chr11-5238497-G-C
• rs2105819
• ENST00000643122.1:c.-28-4036C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643122.1(HBD):​c.-28-4036C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,996 control chromosomes in the GnomAD database, including 21,542 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 0.53 (21542 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 7 publications found

Genes affected

HBD (HGNC:4829): (hemoglobin subunit delta) The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute HbA-2, which with HbF comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5'-epsilon--Ggamma--Agamma--delta--beta-3'. Mutations in the delta-globin gene are associated with beta-thalassemia. [provided by RefSeq, Jul 2008]

HBD Gene-Disease associations (from GenCC):

• delta-beta-thalassemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000298932 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• 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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBD	ENST00000643122.1	c.-28-4036C>G		intron_variant	Intron 1 of 3			ENSP00000494708.1
ENSG00000298932	ENST00000759072.1	n.266-4612G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79974 AN: 151878 Hom.: 21524 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.527 AC: 80039 AN: 151996 Hom.: 21542 Cov.: 32 AF XY: 0.530 AC XY: 39369 AN XY: 74284

African (AFR) AF: 0.525 AC: 21760 AN: 41450

American (AMR) AF: 0.631 AC: 9638 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2268 AN: 3470

East Asian (EAS) AF: 0.779 AC: 4035 AN: 5182

South Asian (SAS) AF: 0.559 AC: 2689 AN: 4814

European-Finnish (FIN) AF: 0.462 AC: 4871 AN: 10544

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32884 AN: 67948

Other (OTH) AF: 0.572 AC: 1207 AN: 2110

Alfa AF: 0.364 Hom.: 933

Bravo AF: 0.538

Asia WGS AF: 0.620 AC: 2157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	9.7
DANN	Benign	0.65
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs2105819; hg19: chr11-5259727;