rs1043526

Variant names:

• chr5-68298496-A-G
• rs1043526
• NM_181523.3:c.*895A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_181523.3(PIK3R1):​c.*895A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 233,218 control chromosomes in the GnomAD database, including 1,515 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 0.097 (926 hom., cov: 32)
  • Exomes 𝑓: 0.11 (589 hom.)
• Consequence: PIK3R1 NM_181523.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.52
• Publications: 19 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R1	NM_181523.3	c.*895A>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000521381.6	NP_852664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6	c.*895A>G		3_prime_UTR_variant	Exon 16 of 16	1	NM_181523.3	ENSP00000428056.1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14721 AN: 152052 Hom.: 927 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.109 AC: 8829 AN: 81050 Hom.: 589 Cov.: 0 AF XY: 0.109 AC XY: 4052 AN XY: 37296

African (AFR) AF: 0.0294 AC: 114 AN: 3880

American (AMR) AF: 0.0893 AC: 223 AN: 2496

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 660 AN: 5110

East Asian (EAS) AF: 0.00150 AC: 17 AN: 11296

South Asian (SAS) AF: 0.0457 AC: 32 AN: 700

European-Finnish (FIN) AF: 0.120 AC: 58 AN: 484

Middle Eastern (MID) AF: 0.128 AC: 62 AN: 486

European-Non Finnish (NFE) AF: 0.138 AC: 6903 AN: 49844

Other (OTH) AF: 0.113 AC: 760 AN: 6754

GnomAD4 genome AF: 0.0967 AC: 14719 AN: 152168 Hom.: 926 Cov.: 32 AF XY: 0.0942 AC XY: 7006 AN XY: 74386

African (AFR) AF: 0.0310 AC: 1287 AN: 41518

American (AMR) AF: 0.108 AC: 1648 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3464

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5180

South Asian (SAS) AF: 0.0493 AC: 238 AN: 4826

European-Finnish (FIN) AF: 0.109 AC: 1157 AN: 10580

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.140 AC: 9512 AN: 67992

Other (OTH) AF: 0.104 AC: 219 AN: 2110

Alfa AF: 0.125 Hom.: 4175

Bravo AF: 0.0927

Asia WGS AF: 0.0410 AC: 142 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		3.5
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: rs1043526; hg19: chr5-67594324; COSMIC: COSV57139879;