5-68291606-A-G

Position:

• chr5-68291606-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_181523.3(PIK3R1):​c.917-653A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 152,264 control chromosomes in the GnomAD database, including 707 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 0.087 (705 hom., cov: 32)
  • Exomes 𝑓: 0.16 (2 hom.)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R1	NM_181523.3	c.917-653A>G		intron_variant		ENST00000521381.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R1	ENST00000521381.6	c.917-653A>G		intron_variant		1	NM_181523.3	P1

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13238 AN: 152096 Hom.: 706 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0956

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0967

GnomAD4 exome AF: 0.160 AC: 8 AN: 50 Hom.: 2 Cov.: 0 AF XY: 0.167 AC XY: 7 AN XY: 42

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0869 AC: 13228 AN: 152214 Hom.: 705 Cov.: 32 AF XY: 0.0871 AC XY: 6480 AN XY: 74426

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.0804

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0946

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0962

Alfa AF: 0.109 Hom.: 978

Bravo AF: 0.0810

Asia WGS AF: 0.0740 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.3
DANN	Benign	0.84

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: rs831125; hg19: chr5-67587434;