5-68288930-A-G

Position:

• chr5-68288930-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181523.3(PIK3R1):​c.917-3329A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,828 control chromosomes in the GnomAD database, including 4,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.22 (4020 hom., cov: 30)
• Consequence: PIK3R1 NM_181523.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.576

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-68288930-A-G is Benign according to our data. Variant chr5-68288930-A-G is described in ClinVar as [Benign]. Clinvar id is 1264402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R1	NM_181523.3	c.917-3329A>G		intron_variant		ENST00000521381.6	NP_852664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R1	ENST00000521381.6	c.917-3329A>G		intron_variant		1	NM_181523.3	ENSP00000428056	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33611 AN: 151710 Hom.: 4015 Cov.: 30

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.222 AC: 33636 AN: 151828 Hom.: 4020 Cov.: 30 AF XY: 0.221 AC XY: 16410 AN XY: 74206

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.233

Alfa AF: 0.228 Hom.: 746

Bravo AF: 0.215

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	16
DANN	Benign	0.72

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: rs1862162; hg19: chr5-67584758; COSMIC: COSV57127117; COSMIC: COSV57127117;