Genetic Variant PIK3R1:p.Phe392Phe (chr5-68293360-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_181523.3(PIK3R1):c.1176C>T(p.Phe392Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,612,240 control chromosomes in the GnomAD database, including 2,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 417 hom., cov: 32)

Exomes 𝑓: 0.027 ( 1722 hom. )

Consequence

PIK3R1
NM_181523.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.50

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]

PIK3R1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 5-68293360-C-T is Benign according to our data. Variant chr5-68293360-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 159720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R1	NM_181523.3 link	c.1176C>T	p.Phe392Phe	synonymous_variant	Exon 10 of 16	ENST00000521381.6	NP_852664.1	P27986-1A0A2X0SFG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6 link	c.1176C>T	p.Phe392Phe	synonymous_variant	Exon 10 of 16	1	NM_181523.3	ENSP00000428056.1		P27986-1

Frequencies

GnomAD3 genomes

AF:

0.0525

AC:

7986

AN:

152126

Hom.:

418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0338

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.0599

GnomAD3 exomes

AF:

0.0530

AC:

13091

AN:

247096

Hom.:

701

AF XY:

0.0524

AC XY:

7042

AN XY:

134480

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.0272

Gnomad ASJ exome

AF:

0.0419

Gnomad EAS exome

AF:

0.175

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0459

GnomAD4 exome

AF:

0.0268

AC:

39059

AN:

1459996

Hom.:

1722

Cov.:

AF XY:

0.0293

AC XY:

21308

AN XY:

726370

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.0277

Gnomad4 ASJ exome

AF:

0.0406

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0221

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.0428

GnomAD4 genome

AF:

0.0525

AC:

7994

AN:

152244

Hom.:

417

Cov.:

AF XY:

0.0531

AC XY:

3952

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0339

Gnomad4 ASJ

AF:

0.0346

Gnomad4 EAS

AF:

0.171

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.0592

Alfa

AF:

0.0305

Hom.:

113

Bravo

AF:

0.0540

Asia WGS

AF:

0.185

AC:

643

AN:

3478

EpiCase

AF:

0.0169

EpiControl

AF:

0.0164

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Oct 31, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SHORT syndrome;C3554689:Agammaglobulinemia 7, autosomal recessive;C4014934:Immunodeficiency 36

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over