chr11-5236808-T-A

Variant names:

• chr11-5236808-T-A
• rs10837643
• ENST00000643122.1:c.-28-2347A>T

Variant summary

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

The ENST00000643122.1(HBD):​c.-28-2347A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 150,788 control chromosomes in the GnomAD database, including 19,793 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 0.51 (19793 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HBD	ENST00000643122.1		c.-28-2347A>T		intron	N/A	ENSP00000494708.1
	ENSG00000298932	ENST00000759072.1		n.266-6301T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76363 AN: 150676 Hom.: 19776 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.507 AC: 76426 AN: 150788 Hom.: 19793 Cov.: 32 AF XY: 0.511 AC XY: 37643 AN XY: 73716

African (AFR) AF: 0.444 AC: 17839 AN: 40206

American (AMR) AF: 0.621 AC: 9492 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3470

East Asian (EAS) AF: 0.779 AC: 4027 AN: 5168

South Asian (SAS) AF: 0.559 AC: 2690 AN: 4814

European-Finnish (FIN) AF: 0.468 AC: 4949 AN: 10578

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.490 AC: 33304 AN: 67964

Other (OTH) AF: 0.556 AC: 1168 AN: 2102

Alfa AF: 0.484 Hom.: 2255

Bravo AF: 0.510

Asia WGS AF: 0.616 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.75
PhyloP100		-0.043

Splicing

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

Other links and lift over

dbSNP: rs10837643; hg19: chr11-5258038;