rs11713445

chr3-130744142-G-A

Variant summary

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

The NM_014602.3(PIK3R4):c.733+344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,096 control chromosomes in the GnomAD database, including 3,182 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 0.20 (3182 hom., cov: 32)
• Consequence: PIK3R4 NM_014602.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

Genes affected

PIK3R4 (HGNC:8982): (phosphoinositide-3-kinase regulatory subunit 4) Predicted to enable protein serine/threonine kinase activity. Involved in positive regulation of phosphatidylinositol 3-kinase activity; receptor catabolic process; and regulation of cytokinesis. Located in late endosome and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R4	NM_014602.3	c.733+344C>T		intron_variant		ENST00000356763.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R4	ENST00000356763.8	c.733+344C>T		intron_variant		1	NM_014602.3	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29915 AN: 151978 Hom.: 3171 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.197 AC: 29950 AN: 152096 Hom.: 3182 Cov.: 32 AF XY: 0.204 AC XY: 15179 AN XY: 74344

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.222

Alfa AF: 0.205 Hom.: 1717

Bravo AF: 0.202

Asia WGS AF: 0.294 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.3
Dann	Benign	0.68

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: rs11713445; hg19: chr3-130462986;