rs1609812
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000518.5(HBB):c.316-185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,150 control chromosomes in the GnomAD database, including 51,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.82 ( 51216 hom., cov: 32)
Consequence
HBB
NM_000518.5 intron
NM_000518.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.59
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 11-5225911-G-A is Benign according to our data. Variant chr11-5225911-G-A is described in ClinVar as [Benign]. Clinvar id is 36316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-5225911-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBB | NM_000518.5 | c.316-185C>T | intron_variant | ENST00000335295.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBB | ENST00000335295.4 | c.316-185C>T | intron_variant | 1 | NM_000518.5 | P1 | |||
HBB | ENST00000647020.1 | c.316-185C>T | intron_variant | P1 | |||||
HBB | ENST00000633227.1 | c.*132-185C>T | intron_variant, NMD_transcript_variant | 3 | |||||
HBB | ENST00000475226.1 | n.248-185C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.816 AC: 124056AN: 152032Hom.: 51185 Cov.: 32
GnomAD3 genomes
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32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.816 AC: 124145AN: 152150Hom.: 51216 Cov.: 32 AF XY: 0.807 AC XY: 60043AN XY: 74374
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
beta Thalassemia Benign:4
Benign, criteria provided, single submitter | clinical testing;curation | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 18, 2011 | - - |
Benign, no assertion criteria provided | research | College of Science, Al Muthanna University, Al Muthanna University | Jan 01, 2018 | - - |
Benign, no assertion criteria provided | curation | The ITHANET community portal, The Cyprus Institute of Neurology and Genetics | Nov 25, 2019 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 15, 2015 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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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