Genetic Variant HBD:c.-29+1898T>G (chr11-5241552-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000643122.1(HBD):c.-29+1898T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,058 control chromosomes in the GnomAD database, including 50,881 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 0.82 ( 50864 hom., cov: 30)

Exomes 𝑓: 0.81 ( 17 hom. )

Consequence

HBD
ENST00000643122.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

3 publications found

Variant links:

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

HBD links:

ENSG00000290652 (HGNC:):

ENSG00000290652 links:

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ACMG classification

Classification was made for transcript

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 = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000643122.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HBD	ENST00000643122.1		c.-29+1898T>G	intron	N/A	ENSP00000494708.1	P02042
ENSG00000290652	ENST00000454892.2	TSL:2	n.1003T>G	non_coding_transcript_exon	Exon 3 of 3
ENSG00000298932	ENST00000759072.1		n.266-1557A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.817

AC:

124108

AN:

151886

Hom.:

50820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.818

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.863

Gnomad ASJ

AF:

0.869

Gnomad EAS

AF:

0.898

Gnomad SAS

AF:

0.832

Gnomad FIN

AF:

0.683

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.857

GnomAD4 exome

AF:

0.815

AC:

AN:

Hom.:

Cov.:

AF XY:

0.813

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AF:

0.833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.590

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.817

AC:

124214

AN:

152004

Hom.:

50864

Cov.:

AF XY:

0.813

AC XY:

60417

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.818

AC:

33881

AN:

41436

American (AMR)

AF:

0.863

AC:

13197

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.869

AC:

3017

AN:

3470

East Asian (EAS)

AF:

0.898

AC:

4638

AN:

5164

South Asian (SAS)

AF:

0.833

AC:

4011

AN:

4818

European-Finnish (FIN)

AF:

0.683

AC:

7210

AN:

10552

Middle Eastern (MID)

AF:

0.871

AC:

256

AN:

294

European-Non Finnish (NFE)

AF:

0.816

AC:

55478

AN:

67962

Other (OTH)

AF:

0.860

AC:

1816

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1180

2359

3539

4718

5898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.816

Hom.:

10270

Bravo

AF:

0.825

Asia WGS

AF:

0.865

AC:

3008

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.48

(source)

DANN

Benign

0.40

PhyloP100

-1.1

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over