rs52911

Variant names:

• chr18-41974975-G-A
• rs52911
• NM_002647.4:c.531+4519G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-41974975-G-A
• chr18-41974975-G-C
• chr18-41974975-G-T

Variant summary

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

The NM_002647.4(PIK3C3):​c.531+4519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,972 control chromosomes in the GnomAD database, including 19,775 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 0.49 (19775 hom., cov: 32)
• Consequence: PIK3C3 NM_002647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 9 publications found

Genes affected

PIK3C3 (HGNC:8974): (phosphatidylinositol 3-kinase catalytic subunit type 3) Enables 1-phosphatidylinositol-3-kinase activity. Involved in early endosome to late endosome transport and regulation of cytokinesis. Acts upstream of or within autophagy and protein lipidation. Located in autolysosome; late endosome; and midbody. [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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002647.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C3	NM_002647.4	MANE Select	c.531+4519G>A		intron	N/A	NP_002638.2
	PIK3C3	NM_001308020.2		c.342+4519G>A		intron	N/A	NP_001294949.1	A8MYT4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C3	ENST00000262039.9	TSL:1 MANE Select	c.531+4519G>A		intron	N/A	ENSP00000262039.3	Q8NEB9
	PIK3C3	ENST00000858068.1		c.531+4519G>A		intron	N/A	ENSP00000528127.1
	PIK3C3	ENST00000858070.1		c.531+4519G>A		intron	N/A	ENSP00000528129.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74277 AN: 151854 Hom.: 19734 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.489 AC: 74376 AN: 151972 Hom.: 19775 Cov.: 32 AF XY: 0.492 AC XY: 36552 AN XY: 74266

African (AFR) AF: 0.704 AC: 29143 AN: 41412

American (AMR) AF: 0.526 AC: 8037 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1177 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3124 AN: 5146

South Asian (SAS) AF: 0.509 AC: 2454 AN: 4818

European-Finnish (FIN) AF: 0.378 AC: 3986 AN: 10558

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24983 AN: 67982

Other (OTH) AF: 0.456 AC: 963 AN: 2112

Alfa AF: 0.429 Hom.: 6355

Bravo AF: 0.510

Asia WGS AF: 0.586 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.95
DANN	Benign	0.43
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: rs52911; hg19: chr18-39554939;