chr1-46135525-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.149
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
P3R3URF-PIK3R3NM_001303427.2 linkuse as main transcriptc.244+40703T>C intron_variant NP_001290356.1 Q68CY7F6TDL0Q7Z3W2B4DXM8
PIK3R3NM_001328648.1 linkuse as main transcriptc.-27+39312T>C intron_variant NP_001315577.1
LOC101929626NR_125987.1 linkuse as main transcriptn.144+871A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
P3R3URF-PIK3R3ENST00000540385.2 linkuse as main transcriptc.244+40703T>C intron_variant 2 ENSP00000439913.1 F6TDL0
ENSG00000227857ENST00000452785.2 linkuse as main transcriptn.124+871A>G intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.684
AC:
103824
AN:
151900
Hom.:
35618
Cov.:
31
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.734
Gnomad4 AMR
AF:
0.670
Gnomad4 ASJ
AF:
0.718
Gnomad4 EAS
AF:
0.700
Gnomad4 SAS
AF:
0.554
Gnomad4 FIN
AF:
0.653
Gnomad4 NFE
AF:
0.666
Gnomad4 OTH
AF:
0.662
Alfa
AF:
0.668
Hom.:
4394
Bravo
AF:
0.690
Asia WGS
AF:
0.642
AC:
2230
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
5.3
DANN
Benign
0.72

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1473840; hg19: chr1-46601197; COSMIC: COSV53106151; COSMIC: COSV53106151; API