chr3-130704514-A-G

Variant names:

• chr3-130704514-A-G
• rs2200368
• NM_014602.3:c.2933-626T>C

Variant summary

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

The NM_014602.3(PIK3R4):​c.2933-626T>C 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 152,132 control chromosomes in the GnomAD database, including 3,483 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 (3483 hom., cov: 32)
• Consequence: PIK3R4 NM_014602.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 3 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R4	NM_014602.3	c.2933-626T>C		intron_variant	Intron 12 of 19	ENST00000356763.8	NP_055417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R4	ENST00000356763.8	c.2933-626T>C		intron_variant	Intron 12 of 19	1	NM_014602.3	ENSP00000349205.3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31260 AN: 152014 Hom.: 3467 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.206 AC: 31306 AN: 152132 Hom.: 3483 Cov.: 32 AF XY: 0.213 AC XY: 15874 AN XY: 74362

African (AFR) AF: 0.156 AC: 6477 AN: 41498

American (AMR) AF: 0.321 AC: 4901 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 828 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1336 AN: 5176

South Asian (SAS) AF: 0.358 AC: 1726 AN: 4818

European-Finnish (FIN) AF: 0.197 AC: 2080 AN: 10572

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13124 AN: 67996

Other (OTH) AF: 0.235 AC: 498 AN: 2116

Alfa AF: 0.206 Hom.: 1792

Bravo AF: 0.212

Asia WGS AF: 0.330 AC: 1146 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.59
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2200368; hg19: chr3-130423358;