rs11650737

Variant names:

Variant summary

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

The NM_001251851.2(PIK3R5):c.-226A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,604,864 control chromosomes in the GnomAD database, including 68,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6344 hom., cov: 33)

Exomes 𝑓: 0.29 ( 62231 hom. )

Consequence

PIK3R5
NM_001251851.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.786

Variant links:

Genes affected

PIK3R5 (HGNC:30035): (phosphoinositide-3-kinase regulatory subunit 5) Phosphatidylinositol 3-kinases (PI3Ks) phosphorylate the inositol ring of phosphatidylinositol at the 3-prime position, and play important roles in cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. The PI3Ks are divided into three classes: I, II and III, and only the class I PI3Ks are involved in oncogenesis. This gene encodes the 101 kD regulatory subunit of the class I PI3K gamma complex, which is a dimeric enzyme, consisting of a 110 kD catalytic subunit gamma and a regulatory subunit of either 55, 87 or 101 kD. This protein recruits the catalytic subunit from the cytosol to the plasma membrane through high-affinity interaction with G-beta-gamma proteins. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been found. [provided by RefSeq, Oct 2011]

PIK3R5 links:

LOC124903922 (HGNC:):

LOC124903922 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=-0.72).

BP6

Variant 17-8888854-T-C is Benign according to our data. Variant chr17-8888854-T-C is described in ClinVar as [Benign]. Clinvar id is 129895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8888854-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R5	NM_001142633.3 link	c.933A>G	p.Leu311Leu	synonymous_variant	Exon 10 of 19	ENST00000447110.6	NP_001136105.1	Q8WYR1-1L7RT34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R5	ENST00000447110.6 link	c.933A>G	p.Leu311Leu	synonymous_variant	Exon 10 of 19	5	NM_001142633.3	ENSP00000392812.1		Q8WYR1-1

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42375

AN:

151962

Hom.:

6327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.299

GnomAD3 exomes

AF:

0.248

AC:

59355

AN:

239436

Hom.:

8501

AF XY:

0.245

AC XY:

31919

AN XY:

130230

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.000713

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.285

AC:

414544

AN:

1452784

Hom.:

62231

Cov.:

AF XY:

0.281

AC XY:

202809

AN XY:

722874

show subpopulations

Gnomad4 AFR exome

AF:

0.292

Gnomad4 AMR exome

AF:

0.251

Gnomad4 ASJ exome

AF:

0.320

Gnomad4 EAS exome

AF:

0.000630

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.275

GnomAD4 genome

AF:

0.279

AC:

42427

AN:

152080

Hom.:

6344

Cov.:

AF XY:

0.269

AC XY:

19969

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.302

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.291

Hom.:

1383

Bravo

AF:

0.289

Asia WGS

AF:

0.0920

AC:

321

AN:

3478

EpiCase

AF:

0.307

EpiControl

AF:

0.310

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ataxia with oculomotor apraxia type 3

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.0

DANN

Benign

0.73

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