rs2105819

Positions:

• chr11-5238497-G-C
• chr11-5238497-G-T

Variant summary

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

The ENST00000643122.1(HBD):​c.-28-4036C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,996 control chromosomes in the GnomAD database, including 21,542 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 (21542 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-1.01).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HBD	ENST00000643122.1	c.-28-4036C>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79974 AN: 151878 Hom.: 21524 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.527 AC: 80039 AN: 151996 Hom.: 21542 Cov.: 32 AF XY: 0.530 AC XY: 39369 AN XY: 74284

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.572

Alfa AF: 0.364 Hom.: 933

Bravo AF: 0.538

Asia WGS AF: 0.620 AC: 2157 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	9.7
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2105819; hg19: chr11-5259727;