5-68224398-G-A

Variant names:

• chr5-68224398-G-A
• rs706711
• NM_181523.3:c.-386-1892G>A

Variant summary

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

The NM_181523.3(PIK3R1):​c.-386-1892G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,006 control chromosomes in the GnomAD database, including 24,029 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 0.54 (24029 hom., cov: 32)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580
• Publications: 7 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R1	NM_181523.3	c.-386-1892G>A		intron_variant	Intron 1 of 15	ENST00000521381.6	NP_852664.1
PIK3R1	XM_005248542.4	c.-386-1892G>A		intron_variant	Intron 1 of 15		XP_005248599.1
PIK3R1	XM_017009585.3	c.-386-1892G>A		intron_variant	Intron 1 of 15		XP_016865074.1
PIK3R1	XM_047417315.1	c.-386-1892G>A		intron_variant	Intron 1 of 15		XP_047273271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6	c.-386-1892G>A		intron_variant	Intron 1 of 15	1	NM_181523.3	ENSP00000428056.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81735 AN: 151888 Hom.: 23960 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.539 AC: 81867 AN: 152006 Hom.: 24029 Cov.: 32 AF XY: 0.534 AC XY: 39700 AN XY: 74278

African (AFR) AF: 0.779 AC: 32336 AN: 41484

American (AMR) AF: 0.501 AC: 7659 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3468

East Asian (EAS) AF: 0.726 AC: 3757 AN: 5178

South Asian (SAS) AF: 0.443 AC: 2129 AN: 4810

European-Finnish (FIN) AF: 0.392 AC: 4130 AN: 10532

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.431 AC: 29282 AN: 67936

Other (OTH) AF: 0.478 AC: 1010 AN: 2112

Alfa AF: 0.543 Hom.: 10612

Bravo AF: 0.561

Asia WGS AF: 0.599 AC: 2079 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.7
DANN	Benign	0.58
PhyloP100		0.58
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: rs706711; hg19: chr5-67520226; COSMIC: COSV57126672; COSMIC: COSV57126672;