chr16-177070-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_000558.5(HBA1):c.237C>T(p.Asn79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 150,438 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 0.000027 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HBA1
NM_000558.5 synonymous
NM_000558.5 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -5.08
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 -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP7
?
Synonymous conserved (PhyloP=-5.08 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBA1 | NM_000558.5 | c.237C>T | p.Asn79= | synonymous_variant | 2/3 | ENST00000320868.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBA1 | ENST00000320868.9 | c.237C>T | p.Asn79= | synonymous_variant | 2/3 | 1 | NM_000558.5 | P1 | |
HBA1 | ENST00000472694.1 | n.373C>T | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
HBA1 | ENST00000487791.1 | n.206C>T | non_coding_transcript_exon_variant | 2/2 | 1 | ||||
HBA1 | ENST00000397797.1 | c.141C>T | p.Asn47= | synonymous_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000266 AC: 4AN: 150438Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000697 AC: 1AN: 143526Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 78184
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000102 AC: 14AN: 1375496Hom.: 0 Cov.: 26 AF XY: 0.00000440 AC XY: 3AN XY: 681874
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GnomAD4 genome ? AF: 0.0000266 AC: 4AN: 150438Hom.: 0 Cov.: 31 AF XY: 0.0000273 AC XY: 2AN XY: 73296
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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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