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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.32
Variant links:
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]

Genome browser will be placed here

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
PIK3R1NM_181523.3 linkuse as main transcriptc.334+14A>C intron_variant ENST00000521381.6 NP_852664.1
PIK3R1XM_005248542.4 linkuse as main transcriptc.334+14A>C intron_variant XP_005248599.1
PIK3R1XM_017009585.3 linkuse as main transcriptc.334+14A>C intron_variant XP_016865074.1
PIK3R1XM_047417315.1 linkuse as main transcriptc.334+14A>C intron_variant XP_047273271.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PIK3R1ENST00000521381.6 linkuse as main transcriptc.334+14A>C intron_variant 1 NM_181523.3 ENSP00000428056 P1P27986-1

Frequencies

GnomAD3 genomes
AF:
0.316
AC:
48083
AN:
151966
Hom.:
8259
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.380
Gnomad AMI
AF:
0.215
Gnomad AMR
AF:
0.336
Gnomad ASJ
AF:
0.226
Gnomad EAS
AF:
0.714
Gnomad SAS
AF:
0.371
Gnomad FIN
AF:
0.270
Gnomad MID
AF:
0.231
Gnomad NFE
AF:
0.253
Gnomad OTH
AF:
0.295
GnomAD3 exomes
AF:
0.324
AC:
72805
AN:
224782
Hom.:
13619
AF XY:
0.317
AC XY:
38786
AN XY:
122348
show subpopulations
Gnomad AFR exome
AF:
0.387
Gnomad AMR exome
AF:
0.380
Gnomad ASJ exome
AF:
0.216
Gnomad EAS exome
AF:
0.722
Gnomad SAS exome
AF:
0.366
Gnomad FIN exome
AF:
0.264
Gnomad NFE exome
AF:
0.247
Gnomad OTH exome
AF:
0.292
GnomAD4 exome
AF:
0.280
AC:
399831
AN:
1426026
Hom.:
61693
Cov.:
29
AF XY:
0.281
AC XY:
198498
AN XY:
707548
show subpopulations
Gnomad4 AFR exome
AF:
0.387
Gnomad4 AMR exome
AF:
0.375
Gnomad4 ASJ exome
AF:
0.222
Gnomad4 EAS exome
AF:
0.724
Gnomad4 SAS exome
AF:
0.366
Gnomad4 FIN exome
AF:
0.265
Gnomad4 NFE exome
AF:
0.253
Gnomad4 OTH exome
AF:
0.301
GnomAD4 genome
AF:
0.317
AC:
48151
AN:
152084
Hom.:
8289
Cov.:
32
AF XY:
0.321
AC XY:
23858
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.380
Gnomad4 AMR
AF:
0.336
Gnomad4 ASJ
AF:
0.226
Gnomad4 EAS
AF:
0.714
Gnomad4 SAS
AF:
0.371
Gnomad4 FIN
AF:
0.270
Gnomad4 NFE
AF:
0.253
Gnomad4 OTH
AF:
0.303
Alfa
AF:
0.283
Hom.:
1854
Bravo
AF:
0.325
Asia WGS
AF:
0.532
AC:
1849
AN:
3478

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 submitterclinical testingGenetic Services Laboratory, University of ChicagoOct 31, 2013- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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 submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanNov 12, 2023This 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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesNov 29, 2023- -
Agammaglobulinemia 7, autosomal recessive Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
SHORT syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
SHORT syndrome;C3554689:Agammaglobulinemia 7, autosomal recessive;C4014934:Immunodeficiency 36 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Immunodeficiency 36 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
12
DANN
Benign
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs706714; hg19: chr5-67522851; COSMIC: COSV57126691; COSMIC: COSV57126691; API