rs785495

Positions:

• chr1-46122215-T-C
• chr1-46122215-T-G

Variant summary

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

The NM_003629.4(PIK3R3):​c.106+9632A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,030 control chromosomes in the GnomAD database, including 15,337 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 0.45 (15337 hom., cov: 32)
• Consequence: PIK3R3 NM_003629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

Genes affected

PIK3R3 (HGNC:8981): (phosphoinositide-3-kinase regulatory subunit 3) Phosphatidylinositol 3-kinase (PI3K) phosphorylates phosphatidylinositol and similar compounds, which then serve as second messengers in growth signaling pathways. PI3K is composed of a catalytic and a regulatory subunit. The protein encoded by this gene represents a regulatory subunit of PI3K. The encoded protein contains two SH2 domains through which it binds activated protein tyrosine kinases to regulate their activity. [provided by RefSeq, Jun 2016]

P3R3URF-PIK3R3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R3	NM_003629.4	c.106+9632A>G		intron_variant		ENST00000262741.10	NP_003620.3
P3R3URF-PIK3R3	NM_001303427.2	c.245-41465A>G		intron_variant			NP_001290356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R3	ENST00000262741.10	c.106+9632A>G		intron_variant		1	NM_003629.4	ENSP00000262741	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67916 AN: 151912 Hom.: 15352 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.447 AC: 67895 AN: 152030 Hom.: 15337 Cov.: 32 AF XY: 0.447 AC XY: 33244 AN XY: 74306

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.437

Alfa AF: 0.441 Hom.: 3181

Bravo AF: 0.451

Asia WGS AF: 0.520 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.93

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: rs785495; hg19: chr1-46587887; COSMIC: COSV53106081;