chr16-176680-A-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_000558.5(HBA1):c.-37A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000032 ( 0 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: -0.985
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBA1 | NM_000558.5 | c.-37A>C | 5_prime_UTR_variant | 1/3 | ENST00000320868.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBA1 | ENST00000320868.9 | c.-37A>C | 5_prime_UTR_variant | 1/3 | 1 | NM_000558.5 | P1 | ||
HBA1 | ENST00000472694.1 | upstream_gene_variant | 1 | ||||||
HBA1 | ENST00000397797.1 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152278Hom.: 0 Cov.: 29
GnomAD3 genomes
?
AF:
AC:
2
AN:
152278
Hom.:
Cov.:
29
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000245 AC: 6AN: 245244Hom.: 0 AF XY: 0.0000375 AC XY: 5AN XY: 133294
GnomAD3 exomes
AF:
AC:
6
AN:
245244
Hom.:
AF XY:
AC XY:
5
AN XY:
133294
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000315 AC: 46AN: 1458670Hom.: 0 Cov.: 30 AF XY: 0.0000317 AC XY: 23AN XY: 725570
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
46
AN:
1458670
Hom.:
Cov.:
30
AF XY:
AC XY:
23
AN XY:
725570
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152278Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 74404
GnomAD4 genome
?
AF:
AC:
2
AN:
152278
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
74404
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
alpha Thalassemia Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Medical Genomics, Royal Prince Alfred Hospital | Nov 23, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at