rs13156223

Variant names:

• chr5-68229712-G-C
• rs13156223
• NM_181523.3:c.334+2703G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181523.3(PIK3R1):​c.334+2703G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,092 control chromosomes in the GnomAD database, including 7,102 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 0.29 (7102 hom., cov: 33)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 6 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R1	NM_181523.3	c.334+2703G>C		intron_variant	Intron 2 of 15	ENST00000521381.6	NP_852664.1
PIK3R1	XM_005248542.4	c.334+2703G>C		intron_variant	Intron 2 of 15		XP_005248599.1
PIK3R1	XM_017009585.3	c.334+2703G>C		intron_variant	Intron 2 of 15		XP_016865074.1
PIK3R1	XM_047417315.1	c.334+2703G>C		intron_variant	Intron 2 of 15		XP_047273271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6	c.334+2703G>C		intron_variant	Intron 2 of 15	1	NM_181523.3	ENSP00000428056.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43906 AN: 151974 Hom.: 7073 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.289 AC: 43970 AN: 152092 Hom.: 7102 Cov.: 33 AF XY: 0.292 AC XY: 21693 AN XY: 74354

African (AFR) AF: 0.342 AC: 14166 AN: 41446

American (AMR) AF: 0.323 AC: 4933 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3468

East Asian (EAS) AF: 0.716 AC: 3707 AN: 5180

South Asian (SAS) AF: 0.357 AC: 1722 AN: 4820

European-Finnish (FIN) AF: 0.214 AC: 2270 AN: 10586

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15714 AN: 67988

Other (OTH) AF: 0.275 AC: 580 AN: 2108

Alfa AF: 0.260 Hom.: 692

Bravo AF: 0.300

Asia WGS AF: 0.523 AC: 1819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.9
DANN	Benign	0.49
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13156223; hg19: chr5-67525540; COSMIC: COSV57126704; COSMIC: COSV57126704;