Variant chr5-68226396-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_181523.3(PIK3R1):c.-280A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 476,310 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.014 ( 54 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 18 hom. )

Consequence

PIK3R1
NM_181523.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.328

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 5-68226396-A-G is Benign according to our data. Variant chr5-68226396-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1204979.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2131/152278) while in subpopulation AFR AF= 0.0491 (2038/41522). AF 95% confidence interval is 0.0473. There are 54 homozygotes in gnomad4. There are 1012 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 54 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PIK3R1	NM_181523.3 linkuse as main transcript	c.-280A>G	5_prime_UTR_variant	2/16	ENST00000521381.6
PIK3R1	XM_005248542.4 linkuse as main transcript	c.-280A>G	5_prime_UTR_variant	2/16
PIK3R1	XM_017009585.3 linkuse as main transcript	c.-280A>G	5_prime_UTR_variant	2/16
PIK3R1	XM_047417315.1 linkuse as main transcript	c.-280A>G	5_prime_UTR_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R1	ENST00000521381.6 linkuse as main transcript	c.-280A>G		5_prime_UTR_variant	2/16	1	NM_181523.3	P1	P27986-1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2129

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0100

GnomAD4 exome

AF:

0.00192

AC:

622

AN:

324032

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

264

AN XY:

166110

show subpopulations

Gnomad4 AFR exome

AF:

0.0481

Gnomad4 AMR exome

AF:

0.00238

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000394

Gnomad4 OTH exome

AF:

0.00375

GnomAD4 genome

AF:

0.0140

AC:

2131

AN:

152278

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1012

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0491

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00872

Hom.:

Bravo

AF:

0.0157

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.4

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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