ENST00000540385.2:c.244+40983T>C

Variant names:

• chr1-46135245-A-G
• rs1707302
• ENST00000540385.2:c.244+40983T>C

Variant summary

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

The ENST00000540385.2(P3R3URF-PIK3R3):​c.244+40983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,988 control chromosomes in the GnomAD database, including 32,142 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 0.65 (32142 hom., cov: 31)
• Consequence: P3R3URF-PIK3R3 ENST00000540385.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 32 publications found

Genes affected

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]

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]

ENSG00000227857 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000540385.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3R3URF-PIK3R3	NM_001303427.2		c.244+40983T>C		intron	N/A	NP_001290356.1
	PIK3R3	NM_001328648.1		c.-27+39592T>C		intron	N/A	NP_001315577.1
	LOC101929626	NR_125987.1		n.144+591A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P3R3URF-PIK3R3	ENST00000540385.2	TSL:2	c.244+40983T>C		intron	N/A	ENSP00000439913.1
	ENSG00000227857	ENST00000452785.3	TSL:2	n.394+591A>G		intron	N/A
	ENSG00000227857	ENST00000756294.1		n.306-350A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98652 AN: 151870 Hom.: 32127 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.649 AC: 98699 AN: 151988 Hom.: 32142 Cov.: 31 AF XY: 0.649 AC XY: 48206 AN XY: 74274

African (AFR) AF: 0.616 AC: 25518 AN: 41448

American (AMR) AF: 0.657 AC: 10031 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2487 AN: 3462

East Asian (EAS) AF: 0.700 AC: 3617 AN: 5166

South Asian (SAS) AF: 0.553 AC: 2665 AN: 4822

European-Finnish (FIN) AF: 0.654 AC: 6901 AN: 10548

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45276 AN: 67966

Other (OTH) AF: 0.645 AC: 1363 AN: 2112

Alfa AF: 0.664 Hom.: 105220

Bravo AF: 0.651

Asia WGS AF: 0.637 AC: 2213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Benign	0.71
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1707302; hg19: chr1-46600917; COSMIC: COSV53106145; COSMIC: COSV53106145;