rs895304

Positions:

• chr5-68296453-G-A

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.1985+112G>A 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 990,694 control chromosomes in the GnomAD database, including 22,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5686 hom., cov: 32)
  • Exomes 𝑓: 0.19 (16891 hom.)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.197

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-68296453-G-A is Benign according to our data. Variant chr5-68296453-G-A is described in ClinVar as [Benign]. Clinvar id is 1261654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R1	NM_181523.3	c.1985+112G>A		intron_variant		ENST00000521381.6	NP_852664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6	c.1985+112G>A		intron_variant		1	NM_181523.3	ENSP00000428056.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37574 AN: 151920 Hom.: 5678 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.192 AC: 160772 AN: 838656 Hom.: 16891 AF XY: 0.189 AC XY: 80855 AN XY: 426798

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.247 AC: 37623 AN: 152038 Hom.: 5686 Cov.: 32 AF XY: 0.247 AC XY: 18326 AN XY: 74332

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.222

Alfa AF: 0.191 Hom.: 1750

Bravo AF: 0.268

Asia WGS AF: 0.298 AC: 1035 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	Jun 26, 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 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.17

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: rs895304; hg19: chr5-67592281; COSMIC: COSV57136851; COSMIC: COSV57136851;