rs831125

Variant names:

• chr5-68291606-A-G
• rs831125
• NM_181523.3:c.917-653A>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.917-653A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 152,264 control chromosomes in the GnomAD database, including 707 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 0.087 (705 hom., cov: 32)
  • Exomes 𝑓: 0.16 (2 hom.)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• 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: 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

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 = 0.113 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.917-653A>G		intron	N/A	NP_852664.1	A0A2X0SFG1
	PIK3R1	NM_181504.4		c.107-653A>G		intron	N/A	NP_852556.2
	PIK3R1	NM_181524.2		c.17-653A>G		intron	N/A	NP_852665.1	P27986-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R1	ENST00000521381.6	TSL:1 MANE Select	c.917-653A>G		intron	N/A	ENSP00000428056.1	P27986-1
	PIK3R1	ENST00000336483.10	TSL:1	c.107-653A>G		intron	N/A	ENSP00000338554.5	P27986-2
	PIK3R1	ENST00000320694.13	TSL:1	c.17-653A>G		intron	N/A	ENSP00000323512.8	P27986-3

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13238 AN: 152096 Hom.: 706 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0956

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0967

GnomAD4 exome AF: 0.160 AC: 8 AN: 50 Hom.: 2 Cov.: 0 AF XY: 0.167 AC XY: 7 AN XY: 42

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 7 AN: 42

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.0869 AC: 13228 AN: 152214 Hom.: 705 Cov.: 32 AF XY: 0.0871 AC XY: 6480 AN XY: 74426

African (AFR) AF: 0.0252 AC: 1047 AN: 41554

American (AMR) AF: 0.0804 AC: 1231 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3468

East Asian (EAS) AF: 0.102 AC: 526 AN: 5174

South Asian (SAS) AF: 0.0946 AC: 456 AN: 4820

European-Finnish (FIN) AF: 0.129 AC: 1363 AN: 10590

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7822 AN: 67990

Other (OTH) AF: 0.0962 AC: 203 AN: 2110

Alfa AF: 0.109 Hom.: 1157

Bravo AF: 0.0810

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.3
DANN	Benign	0.84
PhyloP100		0.43
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: rs831125; hg19: chr5-67587434;