rs706714

Positions:

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

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]

PIK3R1 links:

PIK3R1 (HGNC:):

PIK3R1 links:

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	Effect	MANE	Protein	UniProt
PIK3R1	NM_181523.3 linkuse as main transcript	c.334+14A>C	intron_variant	ENST00000521381.6	NP_852664.1	P27986-1A0A2X0SFG1
PIK3R1	XM_005248542.4 linkuse as main transcript	c.334+14A>C	intron_variant		XP_005248599.1	P27986-1A0A2X0SFG1
PIK3R1	XM_017009585.3 linkuse as main transcript	c.334+14A>C	intron_variant		XP_016865074.1	P27986-1A0A2X0SFG1
PIK3R1	XM_047417315.1 linkuse as main transcript	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 linkuse as main transcript	c.334+14A>C		intron_variant		1	NM_181523.3	ENSP00000428056.1		P27986-1

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

48083

AN:

151966

Hom.:

8259

Cov.:

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.:

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.:

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

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 -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 31, 2013	- -
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

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Agammaglobulinemia 7, autosomal recessive

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

- -

SHORT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

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

-0.76

CADD

Benign

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.

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