rs171649

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181523.3(PIK3R1):c.428-21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,597,208 control chromosomes in the GnomAD database, including 109,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.29 ( 8116 hom., cov: 31)

Exomes 𝑓: 0.37 ( 101117 hom. )

Consequence

PIK3R1
NM_181523.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.138

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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 5-68273918-G-A is Benign according to our data. Variant chr5-68273918-G-A is described in ClinVar as [Benign]. Clinvar id is 1271646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R1	NM_181523.3 link	c.428-21G>A		intron_variant	Intron 3 of 15	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.428-21G>A		intron_variant	Intron 3 of 15	1	NM_181523.3	ENSP00000428056.1		P27986-1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44694

AN:

151964

Hom.:

8120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0735

Gnomad AMI

AF:

0.381

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.302

GnomAD3 exomes

AF:

0.363

AC:

91016

AN:

250972

Hom.:

17431

AF XY:

0.367

AC XY:

49738

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.0698

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.348

Gnomad SAS exome

AF:

0.374

Gnomad FIN exome

AF:

0.405

Gnomad NFE exome

AF:

0.385

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.370

AC:

533983

AN:

1445124

Hom.:

101117

Cov.:

AF XY:

0.371

AC XY:

267106

AN XY:

720022

show subpopulations

Gnomad4 AFR exome

AF:

0.0612

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.353

Gnomad4 EAS exome

AF:

0.380

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.408

Gnomad4 NFE exome

AF:

0.377

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.294

AC:

44679

AN:

152084

Hom.:

8116

Cov.:

AF XY:

0.297

AC XY:

22060

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0733

Gnomad4 AMR

AF:

0.355

Gnomad4 ASJ

AF:

0.353

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.376

Gnomad4 FIN

AF:

0.399

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.303

Alfa

AF:

0.349

Hom.:

2328

Bravo

AF:

0.280

Asia WGS

AF:

0.338

AC:

1174

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

Agammaglobulinemia 7, autosomal recessive

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SHORT syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Immunodeficiency 36

Benign:1

Sep 05, 2021

Genome-Nilou Lab

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

-0.65

CADD

Benign

7.9

DANN

Benign

0.90

BranchPoint Hunter

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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