chr11-5239228-T-C

Variant names:

• chr11-5239228-T-C
• rs968857
• ENST00000643122.1:c.-29+4222A>G

Variant summary

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

The ENST00000643122.1(HBD):​c.-29+4222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,964 control chromosomes in the GnomAD database, including 16,883 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 0.45 (16883 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 21 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 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.-29+4222A>G		intron	N/A	ENSP00000494708.1
	ENSG00000298932	ENST00000759072.1		n.266-3881T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68119 AN: 151844 Hom.: 16873 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.449 AC: 68159 AN: 151964 Hom.: 16883 Cov.: 32 AF XY: 0.455 AC XY: 33765 AN XY: 74246

African (AFR) AF: 0.248 AC: 10285 AN: 41474

American (AMR) AF: 0.592 AC: 9031 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2241 AN: 3468

East Asian (EAS) AF: 0.779 AC: 4014 AN: 5156

South Asian (SAS) AF: 0.558 AC: 2684 AN: 4814

European-Finnish (FIN) AF: 0.469 AC: 4949 AN: 10552

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33188 AN: 67936

Other (OTH) AF: 0.514 AC: 1083 AN: 2108

Alfa AF: 0.425 Hom.: 2062

Bravo AF: 0.451

Asia WGS AF: 0.603 AC: 2093 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.53
PhyloP100		-0.045

Splicing

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

Other links and lift over

dbSNP: rs968857; hg19: chr11-5260458;