chr11-5237362-C-T

Variant names:

• chr11-5237362-C-T
• rs4402323
• ENST00000643122.1:c.-28-2901G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643122.1(HBD):​c.-28-2901G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,964 control chromosomes in the GnomAD database, including 21,726 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 (21726 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 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.-28-2901G>A		intron_variant	Intron 1 of 3			ENSP00000494708.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80379 AN: 151846 Hom.: 21708 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.529 AC: 80446 AN: 151964 Hom.: 21726 Cov.: 32 AF XY: 0.533 AC XY: 39559 AN XY: 74250

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.572

Alfa AF: 0.512 Hom.: 19134

Bravo AF: 0.540

Asia WGS AF: 0.620 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.2
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4402323; hg19: chr11-5258592; COSMIC: COSV53082057; COSMIC: COSV53082057;