rs63749858
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The ENST00000335295.4(HBB):c.431del(p.His144ProfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars). Synonymous variant affecting the same amino acid position (i.e. H144H) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
HBB
ENST00000335295.4 frameshift
ENST00000335295.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.519
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_pathogenic. Variant got 6 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 14 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| HBB | NM_000518.5 | c.431del | p.His144ProfsTer15 | frameshift_variant | 3/3 | ENST00000335295.4 | NP_000509.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| HBB | ENST00000335295.4 | c.431del | p.His144ProfsTer15 | frameshift_variant | 3/3 | 1 | NM_000518.5 | ENSP00000333994 | P1 | |
| HBB | ENST00000647020.1 | c.431del | p.His144ProfsTer15 | frameshift_variant | 3/3 | ENSP00000494175 | P1 | |||
| HBB | ENST00000633227.1 | c.*247del | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 3 | ENSP00000488004 | ||||
| HBB | ENST00000475226.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: other
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
HEMOGLOBIN SAVERNE Other:1
| other, no assertion criteria provided | literature only | OMIM | Dec 12, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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