rs2302974

Positions:

• chr5-68273563-A-C
• chr5-68273563-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181523.3(PIK3R1):​c.427+81A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,185,912 control chromosomes in the GnomAD database, including 24,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3288 hom., cov: 31)
  • Exomes 𝑓: 0.20 (21183 hom.)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.69

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-68273563-A-C is Benign according to our data. Variant chr5-68273563-A-C is described in ClinVar as [Benign]. Clinvar id is 1277601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R1	NM_181523.3	c.427+81A>C		intron_variant		ENST00000521381.6	NP_852664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6	c.427+81A>C		intron_variant		1	NM_181523.3	ENSP00000428056	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31077 AN: 151796 Hom.: 3279 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.199 AC: 206193 AN: 1033998 Hom.: 21183 Cov.: 14 AF XY: 0.200 AC XY: 106558 AN XY: 532608

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.205 AC: 31119 AN: 151914 Hom.: 3288 Cov.: 31 AF XY: 0.206 AC XY: 15282 AN XY: 74250

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.204

Alfa AF: 0.117 Hom.: 189

Bravo AF: 0.198

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.029
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs2302974; hg19: chr5-67569391; COSMIC: COSV57124070;