rs141514155
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000558.5(HBA1):c.*46C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,603,218 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 17 hom., cov: 32)
Exomes 𝑓: 0.013 ( 225 hom. )
Consequence
HBA1
NM_000558.5 3_prime_UTR
NM_000558.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0720
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 16-177457-C-A is Benign according to our data. Variant chr16-177457-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 439094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0117 (1789/152288) while in subpopulation SAS AF= 0.0178 (86/4826). AF 95% confidence interval is 0.0148. There are 17 homozygotes in gnomad4. There are 933 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 17 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBA1 | NM_000558.5 | c.*46C>A | 3_prime_UTR_variant | 3/3 | ENST00000320868.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBA1 | ENST00000320868.9 | c.*46C>A | 3_prime_UTR_variant | 3/3 | 1 | NM_000558.5 | P1 | ||
HBA1 | ENST00000472694.1 | n.611C>A | non_coding_transcript_exon_variant | 2/2 | 1 | ||||
ENST00000702457.1 | n.34G>T | non_coding_transcript_exon_variant | 1/1 | ||||||
HBA1 | ENST00000397797.1 | c.*46C>A | 3_prime_UTR_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0118 AC: 1788AN: 152168Hom.: 17 Cov.: 32
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GnomAD3 exomes AF: 0.0148 AC: 3410AN: 230802Hom.: 51 AF XY: 0.0152 AC XY: 1897AN XY: 125086
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GnomAD4 exome AF: 0.0135 AC: 19522AN: 1450930Hom.: 225 Cov.: 31 AF XY: 0.0140 AC XY: 10076AN XY: 720950
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GnomAD4 genome ? AF: 0.0117 AC: 1789AN: 152288Hom.: 17 Cov.: 32 AF XY: 0.0125 AC XY: 933AN XY: 74492
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
alpha Thalassemia Benign:2
Benign, no assertion criteria provided | curation | The ITHANET community portal, The Cyprus Institute of Neurology and Genetics | Nov 25, 2019 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 09, 2017 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 31, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 14, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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