rs3815701

chr5-68279814-A-Gchr5-68279814-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.634+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,361,854 control chromosomes in the GnomAD database, including 38,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4194 hom., cov: 31)
  • Exomes 𝑓: 0.24 (34627 hom.)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.227

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=-0.92).
• BP6: Variant 5-68279814-A-G is Benign according to our data. Variant chr5-68279814-A-G is described in ClinVar as [Benign]. Clinvar id is 1274836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R1	NM_181523.3	c.634+81A>G		intron_variant		ENST00000521381.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R1	ENST00000521381.6	c.634+81A>G		intron_variant		1	NM_181523.3	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35217 AN: 151948 Hom.: 4188 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.236 AC: 285750 AN: 1209786 Hom.: 34627 AF XY: 0.236 AC XY: 144439 AN XY: 611088

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.232 AC: 35255 AN: 152068 Hom.: 4194 Cov.: 31 AF XY: 0.231 AC XY: 17209 AN XY: 74340

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.232

Alfa AF: 0.231 Hom.: 8471

Bravo AF: 0.228

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied by a panel of primary immunodeficiencies. Number of patients: 39. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.0
Dann	Benign	0.75

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: rs3815701; hg19: chr5-67575642; COSMIC: COSV57127033; COSMIC: COSV57127033;