chr11-5239228-T-C

Variant names:

• chr11-5239228-T-C
• rs968857
• ENST00000643122.1:c.-29+4222A>G

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]

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBD	ENST00000643122.1	c.-29+4222A>G		intron_variant	Intron 1 of 3			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;