22-50456591-C-T
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_002972.4(SBF1):c.3987G>A(p.Ala1329Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,543,372 control chromosomes in the GnomAD database, including 43,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.21 ( 4437 hom., cov: 30)
Exomes 𝑓: 0.22 ( 39330 hom. )
Consequence
SBF1
NM_002972.4 synonymous
NM_002972.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.12
Genes affected
SBF1 (HGNC:10542): (SET binding factor 1) This gene encodes a member of the protein-tyrosine phosphatase family. However, the encoded protein does not appear to be a catalytically active phosphatase because it lacks several amino acids in the catalytic pocket. This protein contains a Guanine nucleotide exchange factor (GEF) domain which is necessary for its role in growth and differentiation. Mutations in this gene have been associated with Charcot-Marie-Tooth disease 4B3. Pseudogenes of this gene have been defined on chromosomes 1 and 8. [provided by RefSeq, Dec 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 22-50456591-C-T is Benign according to our data. Variant chr22-50456591-C-T is described in ClinVar as [Benign]. Clinvar id is 258879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-50456591-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SBF1 | NM_002972.4 | c.3987G>A | p.Ala1329Ala | synonymous_variant | 30/41 | ENST00000380817.8 | NP_002963.2 | |
SBF1 | NM_001410794.1 | c.3990G>A | p.Ala1330Ala | synonymous_variant | 30/41 | NP_001397723.1 | ||
SBF1 | NM_001365819.1 | c.3912G>A | p.Ala1304Ala | synonymous_variant | 29/40 | NP_001352748.1 | ||
SBF1 | NM_001410795.1 | c.3909G>A | p.Ala1303Ala | synonymous_variant | 29/40 | NP_001397724.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SBF1 | ENST00000380817.8 | c.3987G>A | p.Ala1329Ala | synonymous_variant | 30/41 | 1 | NM_002972.4 | ENSP00000370196.2 |
Frequencies
GnomAD3 genomes AF: 0.210 AC: 31911AN: 151890Hom.: 4441 Cov.: 30
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GnomAD3 exomes AF: 0.285 AC: 45396AN: 159552Hom.: 8246 AF XY: 0.277 AC XY: 23801AN XY: 85898
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GnomAD4 exome AF: 0.219 AC: 304539AN: 1391362Hom.: 39330 Cov.: 40 AF XY: 0.219 AC XY: 150160AN XY: 686146
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GnomAD4 genome AF: 0.210 AC: 31916AN: 152010Hom.: 4437 Cov.: 30 AF XY: 0.217 AC XY: 16158AN XY: 74294
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 06, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Charcot-Marie-Tooth disease type 4B3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
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