1-46135525-A-G

Variant names:

• chr1-46135525-A-G
• rs1473840
• ENST00000540385.2:c.244+40703T>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+40703T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,018 control chromosomes in the GnomAD database, including 35,636 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 0.68 (35636 hom., cov: 31)
• Consequence: P3R3URF-PIK3R3 ENST00000540385.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 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+40703T>C		intron	N/A	NP_001290356.1
	PIK3R3	NM_001328648.1		c.-27+39312T>C		intron	N/A	NP_001315577.1
	LOC101929626	NR_125987.1		n.144+871A>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+40703T>C		intron	N/A	ENSP00000439913.1
	ENSG00000227857	ENST00000452785.3	TSL:2	n.394+871A>G		intron	N/A
	ENSG00000227857	ENST00000756294.1		n.306-70A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103824 AN: 151900 Hom.: 35618 Cov.: 31

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.683 AC: 103874 AN: 152018 Hom.: 35636 Cov.: 31 AF XY: 0.681 AC XY: 50619 AN XY: 74296

African (AFR) AF: 0.734 AC: 30437 AN: 41446

American (AMR) AF: 0.670 AC: 10233 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2490 AN: 3468

East Asian (EAS) AF: 0.700 AC: 3624 AN: 5180

South Asian (SAS) AF: 0.554 AC: 2667 AN: 4816

European-Finnish (FIN) AF: 0.653 AC: 6891 AN: 10548

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45288 AN: 67964

Other (OTH) AF: 0.662 AC: 1399 AN: 2114

Alfa AF: 0.690 Hom.: 13715

Bravo AF: 0.690

Asia WGS AF: 0.642 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.72
PhyloP100		0.15
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: rs1473840; hg19: chr1-46601197; COSMIC: COSV53106151; COSMIC: COSV53106151;