rs34309

chr5-68268555-G-A

Variant summary

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

The NM_181523.3(PIK3R1):c.335-4835G>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 152,050 control chromosomes in the GnomAD database, including 8,130 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 (8130 hom., cov: 33)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476

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 = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R1	NM_181523.3	c.335-4835G>A		intron_variant		ENST00000521381.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R1	ENST00000521381.6	c.335-4835G>A		intron_variant		1	NM_181523.3	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44718 AN: 151932 Hom.: 8133 Cov.: 33

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.383

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: 44704 AN: 152050 Hom.: 8130 Cov.: 33 AF XY: 0.297 AC XY: 22079 AN XY: 74302

Gnomad4 AFR AF: 0.0735

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.304

Alfa AF: 0.366 Hom.: 21996

Bravo AF: 0.280

Asia WGS AF: 0.338 AC: 1175 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	3.3
Dann	Benign	0.39

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: rs34309; hg19: chr5-67564383; COSMIC: COSV57126990;