rs901033731
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000518.5(HBB):c.*93A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000605 in 1,156,254 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 (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000050 ( 0 hom. )
Consequence
HBB
NM_000518.5 3_prime_UTR
NM_000518.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0820
Genes affected
HBB (HGNC:4827): (hemoglobin subunit beta) The alpha (HBA) and beta (HBB) loci determine the structure of the 2 types of polypeptide chains in adult hemoglobin, Hb A. The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains. Mutant beta globin causes sickle cell anemia. Absence of beta chain causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. The order of the genes in the beta-globin cluster is 5'-epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBB | NM_000518.5 | c.*93A>T | 3_prime_UTR_variant | 3/3 | ENST00000335295.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBB | ENST00000335295.4 | c.*93A>T | 3_prime_UTR_variant | 3/3 | 1 | NM_000518.5 | P1 | ||
HBB | ENST00000647020.1 | c.*93A>T | 3_prime_UTR_variant | 3/3 | P1 | ||||
HBB | ENST00000633227.1 | c.*353A>T | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 3 | ||||
ENST00000644706.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000498 AC: 5AN: 1004044Hom.: 0 Cov.: 13 AF XY: 0.00000192 AC XY: 1AN XY: 520100
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74372
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 28, 2018 | The HBB c.*93A>T variant (rs901033731), to our knowledge, is not reported in the medical literature or gene specific databases. This variant occurs in the 3' untranslated region at a nucleotide that is weakly conserved. It occurs 15bp upstream of the poly(A) signal, so does not directly alter the signal sequence. It does not introduce any cryptic splice signals. Although there is no evidence predicting that this alteration is deleterious, functional and/or genetic studies would be needed to determine its clinical significance with certainty. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 17, 2024 | Variant summary: HBB c.*93A>T is located in the untranslated mRNA region downstream of the termination codon. The variant was absent in 31406 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.*93A>T in individuals affected with Hemoglobinopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 619851). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 25, 2019 | - - |
Computational scores
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Name
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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