5-68297604-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_181523.3(PIK3R1):c.*3C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00959 in 1,612,452 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 129 hom. )

Consequence

PIK3R1
NM_181523.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.02

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=-0.75).

BP6

Variant 5-68297604-C-T is Benign according to our data. Variant chr5-68297604-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 211905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00967 (1472/152272) while in subpopulation AMR AF= 0.00935 (143/15292). AF 95% confidence interval is 0.00822. There are 16 homozygotes in gnomad4. There are 862 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R1	NM_181523.3 linkuse as main transcript	c.*3C>T		3_prime_UTR_variant	16/16	ENST00000521381.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R1	ENST00000521381.6 linkuse as main transcript	c.*3C>T		3_prime_UTR_variant	16/16	1	NM_181523.3	P1	P27986-1

Frequencies

GnomAD3 genomes

AF:

0.00969

AC:

1474

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.0454

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00882

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0108

AC:

2701

AN:

249326

Hom.:

AF XY:

0.0114

AC XY:

1534

AN XY:

134706

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00496

Gnomad ASJ exome

AF:

0.0299

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00606

Gnomad FIN exome

AF:

0.0426

Gnomad NFE exome

AF:

0.00919

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.00958

AC:

13995

AN:

1460180

Hom.:

129

Cov.:

AF XY:

0.00973

AC XY:

7071

AN XY:

726426

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00550

Gnomad4 ASJ exome

AF:

0.0296

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00637

Gnomad4 FIN exome

AF:

0.0381

Gnomad4 NFE exome

AF:

0.00859

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00967

AC:

1472

AN:

152272

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

862

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00935

Gnomad4 ASJ

AF:

0.0279

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.0454

Gnomad4 NFE

AF:

0.00881

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00946

Hom.:

Bravo

AF:

0.00700

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0141

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 28, 2014

- -

PIK3R1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 09, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

PIK3R1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

Cadd

Benign

Dann

Benign

0.87

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