ENST00000643122.1:c.-28-4077T>C

Variant names:

• chr11-5238538-A-G
• rs10488681
• ENST00000643122.1:c.-28-4077T>C

Variant summary

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

The ENST00000643122.1(HBD):​c.-28-4077T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 152,194 control chromosomes in the GnomAD database, including 1,615 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 0.082 (1615 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.858

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 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.-28-4077T>C		intron_variant	Intron 1 of 3			ENSP00000494708.1

Frequencies

GnomAD3 genomes AF: 0.0817 AC: 12431 AN: 152078 Hom.: 1614 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.0632

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

GnomAD4 genome AF: 0.0818 AC: 12456 AN: 152194 Hom.: 1615 Cov.: 32 AF XY: 0.0786 AC XY: 5852 AN XY: 74424

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00200

Gnomad4 OTH AF: 0.0625

Alfa AF: 0.0539 Hom.: 137

Bravo AF: 0.0907

Asia WGS AF: 0.0180 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10488681; hg19: chr11-5259768;