Variant chr5-68273651-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_181523.3(PIK3R1):c.427+169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 623,802 control chromosomes in the GnomAD database, including 73,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23799 hom., cov: 31)

Exomes 𝑓: 0.45 ( 49355 hom. )

Consequence

PIK3R1
NM_181523.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.378

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=-0.9).

BP6

Variant 5-68273651-A-G is Benign according to our data. Variant chr5-68273651-A-G is described in ClinVar as [Benign]. Clinvar id is 1226091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 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.427+169A>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.427+169A>G		intron_variant		1	NM_181523.3	ENSP00000428056	P1	P27986-1

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81544

AN:

151848

Hom.:

23765

Cov.:

show subpopulations

Gnomad AFR

AF:

0.782

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.460

Gnomad EAS

AF:

0.408

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.449

Gnomad OTH

AF:

0.522

GnomAD4 exome

AF:

0.451

AC:

212736

AN:

471836

Hom.:

49355

Cov.:

AF XY:

0.453

AC XY:

112976

AN XY:

249176

show subpopulations

Gnomad4 AFR exome

AF:

0.779

Gnomad4 AMR exome

AF:

0.318

Gnomad4 ASJ exome

AF:

0.451

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.490

Gnomad4 FIN exome

AF:

0.456

Gnomad4 NFE exome

AF:

0.444

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.537

AC:

81623

AN:

151966

Hom.:

23799

Cov.:

AF XY:

0.535

AC XY:

39726

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.782

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.460

Gnomad4 EAS

AF:

0.407

Gnomad4 SAS

AF:

0.496

Gnomad4 FIN

AF:

0.469

Gnomad4 NFE

AF:

0.450

Gnomad4 OTH

AF:

0.521

Alfa

AF:

0.449

Hom.:

20377

Bravo

AF:

0.538

Asia WGS

AF:

0.520

AC:

1812

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	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.5

DANN

Benign

0.46

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