dbSNP rs2302974: PIK3R1:c.427+81A>C (chr5-68273563-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.69

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
PIK3R1	NM_181523.3 link	c.427+81A>C		intron_variant	Intron 3 of 15	ENST00000521381.6	NP_852664.1	P27986-1A0A2X0SFG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6 link	c.427+81A>C		intron_variant	Intron 3 of 15	1	NM_181523.3	ENSP00000428056.1		P27986-1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31077

AN:

151796

Hom.:

3279

Cov.:

show subpopulations

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.:

AF XY:

0.200

AC XY:

106558

AN XY:

532608

show subpopulations

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.:

AF XY:

0.206

AC XY:

15282

AN XY:

74250

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Jan 24, 2024

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 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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over