Genetic Variant PIK3R1:c.334+22916T>C (chr5-68249925-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181523.3(PIK3R1):c.334+22916T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,228 control chromosomes in the GnomAD database, including 57,893 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.87 ( 57893 hom., cov: 32)

Consequence

PIK3R1
NM_181523.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.605

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 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+22916T>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+22916T>C	intron	N/A	ENSP00000428056.1	P27986-1
PIK3R1	ENST00000517412.2	TSL:1	n.934+22916T>C	intron	N/A
PIK3R1	ENST00000697461.1		c.334+22916T>C	intron	N/A	ENSP00000513319.1	P27986-4

Frequencies

GnomAD3 genomes

AF:

0.869

AC:

132161

AN:

152110

Hom.:

57851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.968

Gnomad AMI

AF:

0.854

Gnomad AMR

AF:

0.760

Gnomad ASJ

AF:

0.824

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.880

Gnomad FIN

AF:

0.893

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.854

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.869

AC:

132253

AN:

152228

Hom.:

57893

Cov.:

AF XY:

0.869

AC XY:

64691

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.968

AC:

40224

AN:

41546

American (AMR)

AF:

0.759

AC:

11607

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.824

AC:

2862

AN:

3472

East Asian (EAS)

AF:

0.777

AC:

4019

AN:

5172

South Asian (SAS)

AF:

0.879

AC:

4241

AN:

4824

European-Finnish (FIN)

AF:

0.893

AC:

9478

AN:

10612

Middle Eastern (MID)

AF:

0.847

AC:

249

AN:

294

European-Non Finnish (NFE)

AF:

0.838

AC:

56991

AN:

67994

Other (OTH)

AF:

0.853

AC:

1803

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

862

1724

2585

3447

4309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.843

Hom.:

28812

Bravo

AF:

0.858

Asia WGS

AF:

0.869

AC:

3025

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.75

PhyloP100

-0.60

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over