rs2431166

Positions:

• chr5-68266615-G-A
• chr5-68266615-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181523.3(PIK3R1):​c.335-6775G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,064 control chromosomes in the GnomAD database, including 8,136 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (8136 hom., cov: 32)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R1	NM_181523.3	c.335-6775G>A		intron_variant		ENST00000521381.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R1	ENST00000521381.6	c.335-6775G>A		intron_variant		1	NM_181523.3	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44752 AN: 151946 Hom.: 8140 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.304

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44737 AN: 152064 Hom.: 8136 Cov.: 32 AF XY: 0.297 AC XY: 22080 AN XY: 74334

Gnomad4 AFR AF: 0.0735

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.304

Alfa AF: 0.234 Hom.: 646

Bravo AF: 0.280

Asia WGS AF: 0.339 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.50

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: rs2431166; hg19: chr5-67562443; COSMIC: COSV57126967;