rs4968596
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The ENST00000336174.12(STRADA):c.36+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,612,884 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0045 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0025 ( 57 hom. )
Consequence
STRADA
ENST00000336174.12 intron
ENST00000336174.12 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.167
Genes affected
STRADA (HGNC:30172): (STE20 related adaptor alpha) The protein encoded by this gene contains a STE20-like kinase domain, but lacks several residues that are critical for catalytic activity, so it is termed a 'pseudokinase'. The protein forms a heterotrimeric complex with serine/threonine kinase 11 (STK11, also known as LKB1) and the scaffolding protein calcium binding protein 39 (CAB39, also known as MO25). The protein activates STK11 leading to the phosphorylation of both proteins and excluding STK11 from the nucleus. The protein is necessary for STK11-induced G1 cell cycle arrest. A mutation in this gene has been shown to result in polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described but their full-length nature is not known. [provided by RefSeq, Sep 2009]
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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=-0.32).
BP6
Variant 17-63728319-T-C is Benign according to our data. Variant chr17-63728319-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 377300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00452 (688/152180) while in subpopulation AMR AF= 0.0147 (225/15272). AF 95% confidence interval is 0.0132. There are 8 homozygotes in gnomad4. There are 464 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STRADA | NM_001003787.4 | c.36+15A>G | intron_variant | ENST00000336174.12 | NP_001003787.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STRADA | ENST00000336174.12 | c.36+15A>G | intron_variant | 1 | NM_001003787.4 | ENSP00000336655 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00452 AC: 687AN: 152062Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00812 AC: 2033AN: 250284Hom.: 35 AF XY: 0.00674 AC XY: 912AN XY: 135356
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GnomAD4 exome AF: 0.00253 AC: 3692AN: 1460704Hom.: 57 Cov.: 30 AF XY: 0.00230 AC XY: 1674AN XY: 726708
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GnomAD4 genome AF: 0.00452 AC: 688AN: 152180Hom.: 8 Cov.: 32 AF XY: 0.00624 AC XY: 464AN XY: 74406
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 16, 2017 | - - |
Polyhydramnios, megalencephaly, and symptomatic epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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