chr16-176702-C-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_000558.5(HBA1):c.-15C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000059 ( 1 hom., cov: 28)
Exomes 𝑓: 0.00015 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
HBA1
NM_000558.5 5_prime_UTR
NM_000558.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.188
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 Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 16-176702-C-G is Benign according to our data. Variant chr16-176702-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2645774.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HBA1 | NM_000558.5 | c.-15C>G | 5_prime_UTR_variant | 1/3 | ENST00000320868.9 | NP_000549.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HBA1 | ENST00000320868.9 | c.-15C>G | 5_prime_UTR_variant | 1/3 | 1 | NM_000558.5 | ENSP00000322421 | P1 | ||
HBA1 | ENST00000472694.1 | n.5C>G | non_coding_transcript_exon_variant | 1/2 | 1 | |||||
HBA1 | ENST00000487791.1 | upstream_gene_variant | 1 | |||||||
HBA1 | ENST00000397797.1 | upstream_gene_variant | 2 | ENSP00000380899 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 6AN: 152280Hom.: 0 Cov.: 28 FAILED QC
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GnomAD3 exomes AF: 0.000162 AC: 39AN: 240656Hom.: 1 AF XY: 0.000222 AC XY: 29AN XY: 130904
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000147 AC: 214AN: 1457026Hom.: 1 Cov.: 31 AF XY: 0.000179 AC XY: 130AN XY: 724598
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000591 AC: 9AN: 152398Hom.: 1 Cov.: 28 AF XY: 0.0000805 AC XY: 6AN XY: 74524
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2022 | HBA1: BS2 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at