rs199530427
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_ModerateBP6_Very_Strong
The NM_181523.3(PIK3R1):c.634+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,613,950 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 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
PIK3R1
NM_181523.3 splice_donor_region, intron
NM_181523.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9695
1
1
Clinical Significance
Conservation
PhyloP100: 1.31
Genes affected
PIK3R1 (HGNC:8979): (phosphoinositide-3-kinase regulatory subunit 1) Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in four transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 5-68279739-T-C is Benign according to our data. Variant chr5-68279739-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 436316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3R1 | NM_181523.3 | c.634+6T>C | splice_donor_region_variant, intron_variant | ENST00000521381.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3R1 | ENST00000521381.6 | c.634+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_181523.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000255 AC: 64AN: 250914Hom.: 0 AF XY: 0.000229 AC XY: 31AN XY: 135664
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GnomAD4 exome AF: 0.000114 AC: 167AN: 1461740Hom.: 0 Cov.: 31 AF XY: 0.000116 AC XY: 84AN XY: 727196
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74356
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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 specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 30, 2017 | - - |
SHORT syndrome;C3554689:Agammaglobulinemia 7, autosomal recessive;C4014934:Immunodeficiency 36 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at