Variant rs2302976 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_181523.3(PIK3R1):c.428-165A>G 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 662,194 control chromosomes in the GnomAD database, including 13,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3326 hom., cov: 32)

Exomes 𝑓: 0.20 ( 10359 hom. )

Consequence

PIK3R1
NM_181523.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.93

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:

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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=-0.71).

BP6

Variant 5-68273774-A-G is Benign according to our data. Variant chr5-68273774-A-G is described in ClinVar as [Benign]. Clinvar id is 1278596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R1	NM_181523.3 linkuse as main transcript	c.428-165A>G		intron_variant		ENST00000521381.6	NP_852664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6 linkuse as main transcript	c.428-165A>G		intron_variant		1	NM_181523.3	ENSP00000428056	P1	P27986-1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31235

AN:

152050

Hom.:

3317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.202

GnomAD4 exome

AF:

0.198

AC:

101148

AN:

510026

Hom.:

10359

Cov.:

AF XY:

0.199

AC XY:

53884

AN XY:

270480

show subpopulations

Gnomad4 AFR exome

AF:

0.221

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.199

Gnomad4 OTH exome

AF:

0.205

GnomAD4 genome

AF:

0.206

AC:

31277

AN:

152168

Hom.:

3326

Cov.:

AF XY:

0.207

AC XY:

15380

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.223

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.221

Gnomad4 EAS

AF:

0.176

Gnomad4 SAS

AF:

0.223

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.202

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.200

Hom.:

5387

Bravo

AF:

0.199

Asia WGS

AF:

0.259

AC:

898

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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