Variant 17-8881044-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001142633.3(PIK3R5):c.2383-27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,561,406 control chromosomes in the GnomAD database, including 74,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7687 hom., cov: 32)

Exomes 𝑓: 0.30 ( 66877 hom. )

Consequence

PIK3R5
NM_001142633.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.05

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:

LOC124903919 (HGNC:):

LOC124903919 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-8881044-A-G is Benign according to our data. Variant chr17-8881044-A-G is described in ClinVar as [Benign]. Clinvar id is 1327033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R5	NM_001142633.3 link	c.2383-27T>C		intron_variant		ENST00000447110.6	NP_001136105.1	Q8WYR1-1L7RT34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R5	ENST00000447110.6 link	c.2383-27T>C		intron_variant		5	NM_001142633.3	ENSP00000392812.1		Q8WYR1-1

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46710

AN:

151860

Hom.:

7665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.348

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.313

GnomAD3 exomes

AF:

0.266

AC:

66590

AN:

250588

Hom.:

10066

AF XY:

0.261

AC XY:

35387

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.356

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.348

Gnomad EAS exome

AF:

0.000816

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.240

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.300

AC:

422890

AN:

1409428

Hom.:

66877

Cov.:

AF XY:

0.295

AC XY:

207950

AN XY:

704186

show subpopulations

Gnomad4 AFR exome

AF:

0.353

Gnomad4 AMR exome

AF:

0.261

Gnomad4 ASJ exome

AF:

0.344

Gnomad4 EAS exome

AF:

0.000685

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.324

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.308

AC:

46764

AN:

151978

Hom.:

7687

Cov.:

AF XY:

0.298

AC XY:

22167

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.349

Gnomad4 AMR

AF:

0.318

Gnomad4 ASJ

AF:

0.359

Gnomad4 EAS

AF:

0.00252

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.316

Hom.:

10599

Bravo

AF:

0.317

Asia WGS

AF:

0.102

AC:

353

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ataxia with oculomotor apraxia type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.010

DANN

Benign

0.40

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