11-5237035-T-C

Variant names:

• chr11-5237035-T-C
• rs3759073
• ENST00000643122.1:c.-28-2574A>G

Variant summary

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

The ENST00000643122.1(HBD):​c.-28-2574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,022 control chromosomes in the GnomAD database, including 25,041 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 0.57 (25041 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 1 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000643122.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBD	ENST00000643122.1		c.-28-2574A>G		intron	N/A	ENSP00000494708.1
	ENSG00000298932	ENST00000759072.1		n.266-6074T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86046 AN: 151904 Hom.: 25010 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.567 AC: 86134 AN: 152022 Hom.: 25041 Cov.: 32 AF XY: 0.568 AC XY: 42206 AN XY: 74308

African (AFR) AF: 0.647 AC: 26803 AN: 41432

American (AMR) AF: 0.648 AC: 9916 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3470

East Asian (EAS) AF: 0.780 AC: 4034 AN: 5170

South Asian (SAS) AF: 0.561 AC: 2704 AN: 4822

European-Finnish (FIN) AF: 0.470 AC: 4965 AN: 10570

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33472 AN: 67948

Other (OTH) AF: 0.602 AC: 1273 AN: 2114

Alfa AF: 0.524 Hom.: 2624

Bravo AF: 0.582

Asia WGS AF: 0.632 AC: 2198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.29
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs3759073; hg19: chr11-5258265;