rs706713

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_181523.3(PIK3R1):c.219C>T(p.Tyr73Tyr) 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:10O:1

Conservation

PhyloP100: -3.30

Publications

59 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 36 with lymphoproliferation
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
SHORT syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
agammaglobulinemia 7, autosomal recessive
Inheritance: AR Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
activated PI3K-delta syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal agammaglobulinemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PIK3R1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
PIK3R1	NM_181523.3 link	c.219C>T	p.Tyr73Tyr	synonymous_variant	Exon 2 of 16	ENST00000521381.6	NP_852664.1	P27986-1A0A2X0SFG1
PIK3R1	XM_005248542.4 link	c.219C>T	p.Tyr73Tyr	synonymous_variant	Exon 2 of 16		XP_005248599.1	P27986-1A0A2X0SFG1
PIK3R1	XM_017009585.3 link	c.219C>T	p.Tyr73Tyr	synonymous_variant	Exon 2 of 16		XP_016865074.1	P27986-1A0A2X0SFG1
PIK3R1	XM_047417315.1 link	c.219C>T	p.Tyr73Tyr	synonymous_variant	Exon 2 of 16		XP_047273271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6 link	c.219C>T	p.Tyr73Tyr	synonymous_variant	Exon 2 of 16	1	NM_181523.3	ENSP00000428056.1		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

GnomAD2 exomes

AF:

0.315

AC:

78832

AN:

250638

AF XY:

0.305

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 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

African (AFR)

AF:

0.420

AC:

14042

AN:

33472

American (AMR)

AF:

0.388

AC:

17335

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

5261

AN:

26132

East Asian (EAS)

AF:

0.708

AC:

28089

AN:

39698

South Asian (SAS)

AF:

0.321

AC:

27731

AN:

86258

European-Finnish (FIN)

AF:

0.261

AC:

13915

AN:

53410

Middle Eastern (MID)

AF:

0.197

AC:

1135

AN:

5768

European-Non Finnish (NFE)

AF:

0.239

AC:

265545

AN:

1111956

Other (OTH)

AF:

0.279

AC:

16873

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

16646

33292

49937

66583

83229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9432

18864

28296

37728

47160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.314

AC:

47699

AN:

151830

Hom.:

8330

Cov.:

AF XY:

0.318

AC XY:

23571

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.410

AC:

16948

AN:

41360

American (AMR)

AF:

0.336

AC:

5125

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

695

AN:

3470

East Asian (EAS)

AF:

0.688

AC:

3549

AN:

5160

South Asian (SAS)

AF:

0.326

AC:

1567

AN:

4810

European-Finnish (FIN)

AF:

0.265

AC:

2786

AN:

10528

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16193

AN:

67928

Other (OTH)

AF:

0.292

AC:

614

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1579

3158

4738

6317

7896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.263

Hom.:

11898

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:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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. -

Nov 23, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 29, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17016694) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:3

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Oct 31, 2013

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 54% of patients studied by a panel of primary immunodeficiencies. Number of patients: 52. Only high quality variants are reported. -

Immunodeficiency 36 with lymphoproliferation

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.24

(source)

DANN

Benign

0.54

PhyloP100

-3.3

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over