rs706714

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

17 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 -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 Benign/Likely_benign. ClinVar VariationId 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.

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.334+14A>C		intron	N/A	NP_852664.1	A0A2X0SFG1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIK3R1	ENST00000521381.6	TSL:1 MANE Select	c.334+14A>C	intron	N/A	ENSP00000428056.1	P27986-1
PIK3R1	ENST00000517412.2	TSL:1	n.934+14A>C	intron	N/A
PIK3R1	ENST00000697461.1		c.334+14A>C	intron	N/A	ENSP00000513319.1	P27986-4

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

GnomAD2 exomes

AF:

0.324

AC:

72805

AN:

224782

AF XY:

0.317

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 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

African (AFR)

AF:

0.387

AC:

12197

AN:

31524

American (AMR)

AF:

0.375

AC:

14087

AN:

37612

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

5394

AN:

24278

East Asian (EAS)

AF:

0.724

AC:

28440

AN:

39298

South Asian (SAS)

AF:

0.366

AC:

29883

AN:

81734

European-Finnish (FIN)

AF:

0.265

AC:

13836

AN:

52238

Middle Eastern (MID)

AF:

0.220

AC:

1227

AN:

5570

European-Non Finnish (NFE)

AF:

0.253

AC:

277103

AN:

1095028

Other (OTH)

AF:

0.301

AC:

17664

AN:

58744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

13848

27696

41543

55391

69239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9838

19676

29514

39352

49190

<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:

0.317

AC:

48151

AN:

152084

Hom.:

8289

Cov.:

AF XY:

0.321

AC XY:

23858

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.380

AC:

15779

AN:

41476

American (AMR)

AF:

0.336

AC:

5130

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

786

AN:

3472

East Asian (EAS)

AF:

0.714

AC:

3689

AN:

5164

South Asian (SAS)

AF:

0.371

AC:

1789

AN:

4822

European-Finnish (FIN)

AF:

0.270

AC:

2856

AN:

10578

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17220

AN:

67980

Other (OTH)

AF:

0.303

AC:

638

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1633

3266

4898

6531

8164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.298

Hom.:

3390

Bravo

AF:

0.325

Asia WGS

AF:

0.532

AC:

1849

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

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

-0.76

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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