rs17318918

chr5-68278091-T-C

Variant summary

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

The NM_181523.3(PIK3R1):c.503-1511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 152,010 control chromosomes in the GnomAD database, including 594 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 0.078 (594 hom., cov: 31)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R1	NM_181523.3	c.503-1511T>C		intron_variant		ENST00000521381.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R1	ENST00000521381.6	c.503-1511T>C		intron_variant		1	NM_181523.3	P1

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11923 AN: 151892 Hom.: 595 Cov.: 31

Gnomad AFR AF: 0.0233

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.00619

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0782

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

GnomAD4 genome AF: 0.0784 AC: 11924 AN: 152010 Hom.: 594 Cov.: 31 AF XY: 0.0793 AC XY: 5890 AN XY: 74276

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.0752

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.00620

Gnomad4 SAS AF: 0.0545

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0779

Alfa AF: 0.103 Hom.: 554

Bravo AF: 0.0719

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.9
Dann	Benign	0.44

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: rs17318918; hg19: chr5-67573919;