11-5237597-G-C

Variant names:

• chr11-5237597-G-C
• rs4910543
• ENST00000643122.1:c.-28-3136C>G

Variant summary

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

The ENST00000643122.1(HBD):​c.-28-3136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,922 control chromosomes in the GnomAD database, including 21,780 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 (21780 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 2 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 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.-28-3136C>G		intron_variant	Intron 1 of 3			ENSP00000494708.1
ENSG00000298932	ENST00000759072.1	n.266-5512G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80464 AN: 151804 Hom.: 21761 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.530 AC: 80532 AN: 151922 Hom.: 21780 Cov.: 32 AF XY: 0.533 AC XY: 39601 AN XY: 74256

African (AFR) AF: 0.526 AC: 21777 AN: 41412

American (AMR) AF: 0.632 AC: 9664 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2262 AN: 3466

East Asian (EAS) AF: 0.778 AC: 4015 AN: 5162

South Asian (SAS) AF: 0.560 AC: 2694 AN: 4814

European-Finnish (FIN) AF: 0.469 AC: 4945 AN: 10552

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33279 AN: 67924

Other (OTH) AF: 0.575 AC: 1209 AN: 2104

Alfa AF: 0.495 Hom.: 2242

Bravo AF: 0.541

Asia WGS AF: 0.621 AC: 2160 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	1.1
DANN	Benign	0.59
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs4910543; hg19: chr11-5258827;