rs35661168
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP5BP4
The ENST00000643122.1(HBD):c.-28-98A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000168 in 596,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000017 ( 0 hom. )
Consequence
HBD
ENST00000643122.1 intron
ENST00000643122.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.12
Publications
2 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-thalassemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-5234559-T-A is Pathogenic according to our data. Variant chr11-5234559-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 15085.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.65). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000168 AC: 1AN: 596456Hom.: 0 Cov.: 6 AF XY: 0.00000310 AC XY: 1AN XY: 322524 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
596456
Hom.:
Cov.:
6
AF XY:
AC XY:
1
AN XY:
322524
show subpopulations
African (AFR)
AF:
AC:
0
AN:
16750
American (AMR)
AF:
AC:
0
AN:
36654
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
20164
East Asian (EAS)
AF:
AC:
0
AN:
33764
South Asian (SAS)
AF:
AC:
0
AN:
65036
European-Finnish (FIN)
AF:
AC:
0
AN:
44796
Middle Eastern (MID)
AF:
AC:
0
AN:
2798
European-Non Finnish (NFE)
AF:
AC:
1
AN:
344602
Other (OTH)
AF:
AC:
0
AN:
31892
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
delta Thalassemia Pathogenic:1
Nov 01, 2002
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
BranchPoint Hunter
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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