rs706713

Positions:

chr5-68226894-C-T

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -3.30

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:

Genome browser will be placed here

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
PIK3R1	NM_181523.3 linkuse as main transcript	c.219C>T	p.Tyr73=	synonymous_variant	2/16	ENST00000521381.6
PIK3R1	XM_005248542.4 linkuse as main transcript	c.219C>T	p.Tyr73=	synonymous_variant	2/16
PIK3R1	XM_017009585.3 linkuse as main transcript	c.219C>T	p.Tyr73=	synonymous_variant	2/16
PIK3R1	XM_047417315.1 linkuse as main transcript	c.219C>T	p.Tyr73=	synonymous_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R1	ENST00000521381.6 linkuse as main transcript	c.219C>T	p.Tyr73=	synonymous_variant	2/16	1	NM_181523.3	P1	P27986-1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47620

AN:

151712

Hom.:

8301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.688

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.285

GnomAD3 exomes

AF:

0.315

AC:

78832

AN:

250638

Hom.:

14537

AF XY:

0.305

AC XY:

41414

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.392

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.700

Gnomad SAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.272

GnomAD4 exome

AF:

0.267

AC:

389926

AN:

1461796

Hom.:

57859

Cov.:

AF XY:

0.266

AC XY:

193195

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.420

Gnomad4 AMR exome

AF:

0.388

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.708

Gnomad4 SAS exome

AF:

0.321

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.279

GnomAD4 genome

AF:

0.314

AC:

47699

AN:

151830

Hom.:

8330

Cov.:

AF XY:

0.318

AC XY:

23571

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.410

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.688

Gnomad4 SAS

AF:

0.326

Gnomad4 FIN

AF:

0.265

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.292

Alfa

AF:

0.252

Hom.:

8591

Bravo

AF:

0.325

Asia WGS

AF:

0.488

AC:

1697

AN:

3478

EpiCase

AF:

0.228

EpiControl

AF:

0.215

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.24

DANN

Benign

0.54

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