rs121913128
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_000558.5(HBA1):c.424_426del(p.Arg142del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
HBA1
NM_000558.5 inframe_deletion
NM_000558.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.06
Genes affected
HBA1 (HGNC:4823): (hemoglobin subunit alpha 1) The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5'- zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta - 3'. The alpha-2 (HBA2) and alpha-1 (HBA1) coding sequences are identical. These genes differ slightly over the 5' untranslated regions and the introns, but they differ significantly over the 3' untranslated regions. Two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin; alpha chains combine with delta chains to constitute HbA-2, which with HbF (fetal hemoglobin) makes up the remaining 3% of adult hemoglobin. Alpha thalassemias result from deletions of each of the alpha genes as well as deletions of both HBA2 and HBA1; some nondeletion alpha thalassemias have also been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_000558.5
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000558.5. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| HBA1 | NM_000558.5 | c.424_426del | p.Arg142del | inframe_deletion | 3/3 | ENST00000320868.9 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HBA1 | ENST00000320868.9 | c.424_426del | p.Arg142del | inframe_deletion | 3/3 | 1 | NM_000558.5 | P1 | |
| HBA1 | ENST00000472694.1 | n.560_562del | non_coding_transcript_exon_variant | 2/2 | 1 | ||||
| ENST00000702457.1 | n.83_85del | non_coding_transcript_exon_variant | 1/1 | ||||||
| HBA1 | ENST00000397797.1 | c.328_330del | p.Arg110del | inframe_deletion | 3/3 | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: other
Submissions summary: Other:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
HEMOGLOBIN KOELLIKER Other:1
| other, no assertion criteria provided | literature only | OMIM | May 10, 2018 | - - |
HEMOGLOBIN F (KOELLIKER) Other:1
| other, no assertion criteria provided | literature only | OMIM | May 10, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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