5-68279516-A-G

Variant names:

• chr5-68279516-A-G
• rs16897620
• NM_181523.3:c.503-86A>G

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.503-86A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 961,532 control chromosomes in the GnomAD database, including 27,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (3867 hom., cov: 30)
  • Exomes 𝑓: 0.23 (23827 hom.)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.44

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 5-68279516-A-G is Benign according to our data. Variant chr5-68279516-A-G is described in ClinVar as [Benign]. Clinvar id is 1241349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R1	NM_181523.3	c.503-86A>G		intron_variant	Intron 4 of 15	ENST00000521381.6	NP_852664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6	c.503-86A>G		intron_variant	Intron 4 of 15	1	NM_181523.3	ENSP00000428056.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 33510 AN: 148244 Hom.: 3862 Cov.: 30

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.230 AC: 186872 AN: 813190 Hom.: 23827 AF XY: 0.230 AC XY: 95483 AN XY: 414796

Gnomad4 AFR exome AF: 0.181

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.226 AC: 33542 AN: 148342 Hom.: 3867 Cov.: 30 AF XY: 0.227 AC XY: 16334 AN XY: 72104

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.231

Alfa AF: 0.218 Hom.: 673

Bravo AF: 0.218

Asia WGS AF: 0.265 AC: 917 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.53
DANN	Benign	0.29

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: rs16897620; hg19: chr5-67575344;