11-5239228-T-C

Position:

• chr11-5239228-T-C

Variant summary

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

The ENST00000643122.1(HBD):​c.-29+4222A>G 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 151,964 control chromosomes in the GnomAD database, including 16,883 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 (16883 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.5239228T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBD	ENST00000643122.1	c.-29+4222A>G		intron_variant				ENSP00000494708.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68119 AN: 151844 Hom.: 16873 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.633

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: 68159 AN: 151964 Hom.: 16883 Cov.: 32 AF XY: 0.455 AC XY: 33765 AN XY: 74246

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.514

Alfa AF: 0.425 Hom.: 2062

Bravo AF: 0.451

Asia WGS AF: 0.603 AC: 2093 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs968857; hg19: chr11-5260458;