rs35278874
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000518.5(HBB):c.174C>T(p.Asn58Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,872 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HBB
NM_000518.5 synonymous
NM_000518.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.246
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 was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 11-5226718-G-A is Benign according to our data. Variant chr11-5226718-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 439138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.246 with no splicing effect.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
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152106
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32
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GnomAD2 exomes AF: 0.0000119 AC: 3AN: 251436 AF XY: 0.00 show subpopulations
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461872Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 727244 show subpopulations
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44724
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8
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26136
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39700
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86258
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53414
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1111996
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60396
Heterozygous variant carriers
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74294 show subpopulations
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
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74294
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0.000288184
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Jan 09, 2023
Quest Diagnostics Nichols Institute San Juan Capistrano
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Feb 08, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not specified Benign:1
Aug 28, 2019
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
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