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:11O: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: Labcorp Genetics (formerly Invitae), Ambry Genetics
PIK3R1-related immunodeficiency and SHORT syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
SHORT syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen
agammaglobulinemia 7, autosomal recessive
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181523.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R1	NM_181523.3	MANE Select	c.219C>T	p.Tyr73Tyr	synonymous	Exon 2 of 16	NP_852664.1	A0A2X0SFG1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3R1	ENST00000521381.6	TSL:1 MANE Select	c.219C>T	p.Tyr73Tyr	synonymous	Exon 2 of 16	ENSP00000428056.1	P27986-1
PIK3R1	ENST00000517412.2	TSL:1	n.819C>T		non_coding_transcript_exon	Exon 2 of 3
PIK3R1	ENST00000697461.1		c.219C>T	p.Tyr73Tyr	synonymous	Exon 2 of 16	ENSP00000513319.1	P27986-4

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (4)

Agammaglobulinemia 7, autosomal recessive (1)

Immunodeficiency 36 with lymphoproliferation (1)

SHORT syndrome (1)

SHORT syndrome;C3554689:Agammaglobulinemia 7, autosomal recessive;C4014934:Immunodeficiency 36 with lymphoproliferation (1)

Computational scores

Source: dbNSFP v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over