rs706714
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_181523.3(PIK3R1):c.334+14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,578,110 control chromosomes in the GnomAD database, including 69,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.32 ( 8289 hom., cov: 32)
Exomes 𝑓: 0.28 ( 61693 hom. )
Consequence
PIK3R1
NM_181523.3 intron
NM_181523.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.32
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 5-68227023-A-C is Benign according to our data. Variant chr5-68227023-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 159723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIK3R1 | NM_181523.3 | c.334+14A>C | intron_variant | ENST00000521381.6 | NP_852664.1 | |||
PIK3R1 | XM_005248542.4 | c.334+14A>C | intron_variant | XP_005248599.1 | ||||
PIK3R1 | XM_017009585.3 | c.334+14A>C | intron_variant | XP_016865074.1 | ||||
PIK3R1 | XM_047417315.1 | c.334+14A>C | intron_variant | XP_047273271.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIK3R1 | ENST00000521381.6 | c.334+14A>C | intron_variant | 1 | NM_181523.3 | ENSP00000428056 | P1 |
Frequencies
GnomAD3 genomes AF: 0.316 AC: 48083AN: 151966Hom.: 8259 Cov.: 32
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GnomAD3 exomes AF: 0.324 AC: 72805AN: 224782Hom.: 13619 AF XY: 0.317 AC XY: 38786AN XY: 122348
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GnomAD4 exome AF: 0.280 AC: 399831AN: 1426026Hom.: 61693 Cov.: 29 AF XY: 0.281 AC XY: 198498AN XY: 707548
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GnomAD4 genome AF: 0.317 AC: 48151AN: 152084Hom.: 8289 Cov.: 32 AF XY: 0.321 AC XY: 23858AN XY: 74352
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 31, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 54% of patients studied by a panel of primary immunodeficiencies. Number of patients: 52. Only high quality variants are reported. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Agammaglobulinemia 7, autosomal recessive Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
SHORT syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
SHORT syndrome;C3554689:Agammaglobulinemia 7, autosomal recessive;C4014934:Immunodeficiency 36 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Immunodeficiency 36 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at