dbSNP rs3730073: PIK3R1:c.1985+124A>C (chr5-68296465-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_181523.3(PIK3R1):c.1985+124A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 878,750 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 57 hom., cov: 32)

Exomes 𝑓: 0.024 ( 325 hom. )

Consequence

PIK3R1
NM_181523.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.163

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=-0.87).

BP6

Variant 5-68296465-A-C is Benign according to our data. Variant chr5-68296465-A-C is described in ClinVar as [Benign]. Clinvar id is 1247789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.021 (3203/152316) while in subpopulation NFE AF= 0.0252 (1716/68032). AF 95% confidence interval is 0.0242. There are 57 homozygotes in gnomad4. There are 1714 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R1	NM_181523.3 link	c.1985+124A>C		intron_variant	Intron 15 of 15	ENST00000521381.6	NP_852664.1	P27986-1A0A2X0SFG1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6 link	c.1985+124A>C		intron_variant	Intron 15 of 15	1	NM_181523.3	ENSP00000428056.1		P27986-1

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3204

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00470

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0602

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0252

Gnomad OTH

AF:

0.0254

GnomAD4 exome

AF:

0.0237

AC:

17195

AN:

726434

Hom.:

325

AF XY:

0.0234

AC XY:

8700

AN XY:

371484

show subpopulations

Gnomad4 AFR exome

AF:

0.00387

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.0512

Gnomad4 EAS exome

AF:

0.0000580

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.0497

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0231

GnomAD4 genome

AF:

0.0210

AC:

3203

AN:

152316

Hom.:

Cov.:

AF XY:

0.0230

AC XY:

1714

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00469

Gnomad4 AMR

AF:

0.0222

Gnomad4 ASJ

AF:

0.0545

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.0602

Gnomad4 NFE

AF:

0.0252

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.00982

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.00289

AC:

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

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.076

DANN

Benign

0.52

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