rs706713
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_181523.3(PIK3R1):c.219C>T(p.Tyr73=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,613,626 control chromosomes in the GnomAD database, including 66,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.31 ( 8330 hom., cov: 31)
Exomes 𝑓: 0.27 ( 57859 hom. )
Consequence
PIK3R1
NM_181523.3 synonymous
NM_181523.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.30
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 5-68226894-C-T is Benign according to our data. Variant chr5-68226894-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 159722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.3 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3R1 | NM_181523.3 | c.219C>T | p.Tyr73= | synonymous_variant | 2/16 | ENST00000521381.6 | |
PIK3R1 | XM_005248542.4 | c.219C>T | p.Tyr73= | synonymous_variant | 2/16 | ||
PIK3R1 | XM_017009585.3 | c.219C>T | p.Tyr73= | synonymous_variant | 2/16 | ||
PIK3R1 | XM_047417315.1 | c.219C>T | p.Tyr73= | synonymous_variant | 2/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3R1 | ENST00000521381.6 | c.219C>T | p.Tyr73= | synonymous_variant | 2/16 | 1 | NM_181523.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.314 AC: 47620AN: 151712Hom.: 8301 Cov.: 31
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GnomAD3 exomes AF: 0.315 AC: 78832AN: 250638Hom.: 14537 AF XY: 0.305 AC XY: 41414AN XY: 135752
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GnomAD4 exome AF: 0.267 AC: 389926AN: 1461796Hom.: 57859 Cov.: 35 AF XY: 0.266 AC XY: 193195AN XY: 727212
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GnomAD4 genome ? AF: 0.314 AC: 47699AN: 151830Hom.: 8330 Cov.: 31 AF XY: 0.318 AC XY: 23571AN XY: 74178
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
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. - |
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 - |
not provided Benign:2Other:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2018 | This variant is associated with the following publications: (PMID: 17016694) - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. - |
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 | Invitae | 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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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
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