rs1043526

Positions:

• chr5-68298496-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.*895A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 233,218 control chromosomes in the GnomAD database, including 1,515 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 0.097 (926 hom., cov: 32)
  • Exomes 𝑓: 0.11 (589 hom.)
• Consequence: PIK3R1 NM_181523.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.52

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 = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R1	NM_181523.3	c.*895A>G		3_prime_UTR_variant	16/16	ENST00000521381.6	NP_852664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6	c.*895A>G		3_prime_UTR_variant	16/16	1	NM_181523.3	ENSP00000428056	P1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14721 AN: 152052 Hom.: 927 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.109 AC: 8829 AN: 81050 Hom.: 589 Cov.: 0 AF XY: 0.109 AC XY: 4052 AN XY: 37296

Gnomad4 AFR exome AF: 0.0294

Gnomad4 AMR exome AF: 0.0893

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.00150

Gnomad4 SAS exome AF: 0.0457

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.0967 AC: 14719 AN: 152168 Hom.: 926 Cov.: 32 AF XY: 0.0942 AC XY: 7006 AN XY: 74386

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00579

Gnomad4 SAS AF: 0.0493

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.104

Alfa AF: 0.130 Hom.: 1927

Bravo AF: 0.0927

Asia WGS AF: 0.0410 AC: 142 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.89

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: rs1043526; hg19: chr5-67594324; COSMIC: COSV57139879; COSMIC: COSV57139879;