rs571422135
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000558.5(HBA1):c.301-17C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,613,276 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 5 hom. )
Consequence
HBA1
NM_000558.5 splice_polypyrimidine_tract, intron
NM_000558.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.06
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 Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 16-177266-C-A is Benign according to our data. Variant chr16-177266-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 439097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAdExome4 at 5 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBA1 | NM_000558.5 | c.301-17C>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000320868.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBA1 | ENST00000320868.9 | c.301-17C>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000558.5 | P1 | |||
ENST00000702457.1 | downstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152240Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000246 AC: 61AN: 248242Hom.: 3 AF XY: 0.000334 AC XY: 45AN XY: 134908
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GnomAD4 exome AF: 0.000121 AC: 177AN: 1460916Hom.: 5 Cov.: 32 AF XY: 0.000176 AC XY: 128AN XY: 726790
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GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152360Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74506
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | May 06, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 20, 2023 | - - |
Computational scores
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Name
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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