3-130709302-C-T

Position:

• chr3-130709302-C-T

Variant summary

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

The NM_014602.3(PIK3R4):​c.2332-810G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,962 control chromosomes in the GnomAD database, including 3,468 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 0.21 (3468 hom., cov: 32)
• Consequence: PIK3R4 NM_014602.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R4	NM_014602.3	c.2332-810G>A		intron_variant		ENST00000356763.8	NP_055417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R4	ENST00000356763.8	c.2332-810G>A		intron_variant		1	NM_014602.3	ENSP00000349205.3
PIK3R4	ENST00000508273.5	c.409-810G>A		intron_variant		3		ENSP00000427302.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31232 AN: 151844 Hom.: 3452 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.206 AC: 31278 AN: 151962 Hom.: 3468 Cov.: 32 AF XY: 0.214 AC XY: 15863 AN XY: 74258

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.233

Alfa AF: 0.206 Hom.: 3362

Bravo AF: 0.212

Asia WGS AF: 0.330 AC: 1147 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.43

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: rs10934954; hg19: chr3-130428146;