chr1-46072368-A-T

Variant names:

• chr1-46072368-A-T
• rs809775
• NM_003629.4:c.314+5147T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003629.4(PIK3R3):​c.314+5147T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,078 control chromosomes in the GnomAD database, including 16,117 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 0.46 (16117 hom., cov: 32)
• Consequence: PIK3R3 NM_003629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 8 publications found

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:54999): (P3R3URF-PIK3R3 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring genes LOC110117498 and PIK3R3. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R3	NM_003629.4	c.314+5147T>A		intron_variant	Intron 3 of 9	ENST00000262741.10	NP_003620.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R3	ENST00000262741.10	c.314+5147T>A		intron_variant	Intron 3 of 9	1	NM_003629.4	ENSP00000262741.5
P3R3URF-PIK3R3	ENST00000540385.2	c.452+5147T>A		intron_variant	Intron 3 of 9	2		ENSP00000439913.1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69702 AN: 151960 Hom.: 16134 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.458 AC: 69682 AN: 152078 Hom.: 16117 Cov.: 32 AF XY: 0.459 AC XY: 34102 AN XY: 74348

African (AFR) AF: 0.457 AC: 18974 AN: 41484

American (AMR) AF: 0.497 AC: 7600 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1718 AN: 3470

East Asian (EAS) AF: 0.616 AC: 3187 AN: 5170

South Asian (SAS) AF: 0.445 AC: 2139 AN: 4808

European-Finnish (FIN) AF: 0.418 AC: 4424 AN: 10582

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30166 AN: 67962

Other (OTH) AF: 0.444 AC: 939 AN: 2114

Alfa AF: 0.448 Hom.: 1907

Bravo AF: 0.464

Asia WGS AF: 0.522 AC: 1811 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.78
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs809775; hg19: chr1-46538040; COSMIC: COSV53105820;