16-173540-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_000517.6(HBA2):c.369C>T(p.His123=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000673 in 148,608 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000067 ( 0 hom., cov: 25)
Consequence
HBA2
NM_000517.6 synonymous
NM_000517.6 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.38
Genes affected
HBA2 (HGNC:4824): (hemoglobin subunit alpha 2) 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 Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP7
?
Synonymous conserved (PhyloP=-1.38 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBA2 | NM_000517.6 | c.369C>T | p.His123= | synonymous_variant | 3/3 | ENST00000251595.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBA2 | ENST00000251595.11 | c.369C>T | p.His123= | synonymous_variant | 3/3 | 1 | NM_000517.6 | P1 | |
HBA2 | ENST00000482565.1 | n.505C>T | non_coding_transcript_exon_variant | 2/2 | 1 | ||||
ENST00000702607.1 | n.121G>A | non_coding_transcript_exon_variant | 1/1 | ||||||
HBA2 | ENST00000397806.1 | c.273C>T | p.His91= | synonymous_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000673 AC: 1AN: 148608Hom.: 0 Cov.: 25
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GnomAD4 exome Cov.: 33
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33
GnomAD4 genome ? AF: 0.00000673 AC: 1AN: 148608Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 72506
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at