rs10837643

Variant names:

• chr11-5236808-T-A
• rs10837643
• ENST00000643122.1:c.-28-2347A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-5236808-T-A
• chr11-5236808-T-C
• chr11-5236808-T-G

Variant summary

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

The ENST00000643122.1(HBD):​c.-28-2347A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 150,788 control chromosomes in the GnomAD database, including 19,793 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 0.51 (19793 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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=-0.86).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBD	ENST00000643122.1	c.-28-2347A>T		intron_variant	Intron 1 of 3			ENSP00000494708.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76363 AN: 150676 Hom.: 19776 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.507 AC: 76426 AN: 150788 Hom.: 19793 Cov.: 32 AF XY: 0.511 AC XY: 37643 AN XY: 73716

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.556

Alfa AF: 0.484 Hom.: 2255

Bravo AF: 0.510

Asia WGS AF: 0.616 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10837643; hg19: chr11-5258038;