rs3730073

chr5-68296465-A-Cchr5-68296465-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.163

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R1	NM_181523.3	c.1985+124A>C		intron_variant		ENST00000521381.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R1	ENST00000521381.6	c.1985+124A>C		intron_variant		1	NM_181523.3	P1

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3204 AN: 152198 Hom.: 57 Cov.: 32

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

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.: 57 Cov.: 32 AF XY: 0.0230 AC XY: 1714 AN XY: 74478

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.: 4

Bravo AF: 0.0175

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

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

Other links and lift over

dbSNP: rs3730073; hg19: chr5-67592293;