rs968856

Variant names:

• chr11-5239346-T-C
• rs968856
• ENST00000643122.1:c.-29+4104A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-5239346-T-C
• chr11-5239346-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643122.1(HBD):​c.-29+4104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,958 control chromosomes in the GnomAD database, including 17,611 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 0.47 (17611 hom., cov: 32)
• Consequence: HBD ENST00000643122.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851
• Publications: 6 publications found

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]

HBD Gene-Disease associations (from GenCC):

• delta-beta-thalassemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000298932 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 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+4104A>G		intron_variant	Intron 1 of 3			ENSP00000494708.1
ENSG00000298932	ENST00000759072.1	n.266-3763T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70603 AN: 151838 Hom.: 17597 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.465 AC: 70668 AN: 151958 Hom.: 17611 Cov.: 32 AF XY: 0.471 AC XY: 34975 AN XY: 74260

African (AFR) AF: 0.305 AC: 12658 AN: 41482

American (AMR) AF: 0.597 AC: 9120 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2245 AN: 3468

East Asian (EAS) AF: 0.780 AC: 4014 AN: 5148

South Asian (SAS) AF: 0.558 AC: 2682 AN: 4808

European-Finnish (FIN) AF: 0.468 AC: 4932 AN: 10534

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33210 AN: 67932

Other (OTH) AF: 0.531 AC: 1122 AN: 2112

Alfa AF: 0.487 Hom.: 7721

Bravo AF: 0.469

Asia WGS AF: 0.609 AC: 2110 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.72
PhyloP100		0.85

Splicing

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

Other links and lift over

dbSNP: rs968856; hg19: chr11-5260576;