Variant chr17-8880832-T-C 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.2496-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,612,472 control chromosomes in the GnomAD database, including 62,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7170 hom., cov: 33)

Exomes 𝑓: 0.27 ( 55449 hom. )

Consequence

PIK3R5
NM_001142633.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.407

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:

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=-0.88).

BP6

Variant 17-8880832-T-C is Benign according to our data. Variant chr17-8880832-T-C is described in ClinVar as [Benign]. Clinvar id is 1327032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R5	NM_001142633.3 linkuse as main transcript	c.2496-46A>G		intron_variant		ENST00000447110.6	NP_001136105.1
LOC124903919	XR_007065610.1 linkuse as main transcript	n.923+2528T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R5	ENST00000447110.6 linkuse as main transcript	c.2496-46A>G		intron_variant		5	NM_001142633.3	ENSP00000392812	P4	Q8WYR1-1

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44552

AN:

152034

Hom.:

7145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.327

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.283

GnomAD3 exomes

AF:

0.242

AC:

60171

AN:

248726

Hom.:

8357

AF XY:

0.236

AC XY:

31728

AN XY:

134488

show subpopulations

Gnomad AFR exome

AF:

0.388

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.318

Gnomad EAS exome

AF:

0.000766

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.268

AC:

391438

AN:

1460320

Hom.:

55449

Cov.:

AF XY:

0.263

AC XY:

191218

AN XY:

726380

show subpopulations

Gnomad4 AFR exome

AF:

0.387

Gnomad4 AMR exome

AF:

0.240

Gnomad4 ASJ exome

AF:

0.312

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.227

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.293

AC:

44614

AN:

152152

Hom.:

7170

Cov.:

AF XY:

0.284

AC XY:

21151

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.381

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.327

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.218

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.289

Hom.:

7298

Bravo

AF:

0.304

Asia WGS

AF:

0.0880

AC:

308

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

-0.88

CADD

Benign

5.2

DANN

Benign

0.81

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