rs4320977

Variant names:

• chr11-5236932-A-G
• rs4320977
• ENST00000643122.1:c.-28-2471T>C

Variant summary

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

The ENST00000643122.1(HBD):​c.-28-2471T>C 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 151,972 control chromosomes in the GnomAD database, including 16,914 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 (16914 hom., cov: 31)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740
• Publications: 5 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 = 0.759 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.-28-2471T>C		intron_variant	Intron 1 of 3			ENSP00000494708.1
ENSG00000298932	ENST00000759072.1	n.266-6177A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68211 AN: 151854 Hom.: 16904 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.636

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: 68250 AN: 151972 Hom.: 16914 Cov.: 31 AF XY: 0.455 AC XY: 33815 AN XY: 74278

African (AFR) AF: 0.249 AC: 10329 AN: 41444

American (AMR) AF: 0.592 AC: 9046 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2243 AN: 3472

East Asian (EAS) AF: 0.779 AC: 4019 AN: 5156

South Asian (SAS) AF: 0.557 AC: 2681 AN: 4814

European-Finnish (FIN) AF: 0.467 AC: 4934 AN: 10558

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33232 AN: 67934

Other (OTH) AF: 0.513 AC: 1081 AN: 2106

Alfa AF: 0.490 Hom.: 23834

Bravo AF: 0.451

Asia WGS AF: 0.603 AC: 2096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.2
DANN	Benign	0.65
PhyloP100		0.74

Splicing

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

Other links and lift over

dbSNP: rs4320977; hg19: chr11-5258162;