chr18-41992294-G-A

Variant names:

• chr18-41992294-G-A
• rs649610
• NM_002647.4:c.715-976G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002647.4(PIK3C3):​c.715-976G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,970 control chromosomes in the GnomAD database, including 20,158 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 (20158 hom., cov: 32)
• Consequence: PIK3C3 NM_002647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C3	NM_002647.4	MANE Select	c.715-976G>A		intron	N/A	NP_002638.2
	PIK3C3	NM_001308020.2		c.526-976G>A		intron	N/A	NP_001294949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C3	ENST00000262039.9	TSL:1 MANE Select	c.715-976G>A		intron	N/A	ENSP00000262039.3
	PIK3C3	ENST00000398870.7	TSL:2	c.526-976G>A		intron	N/A	ENSP00000381845.2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74809 AN: 151852 Hom.: 20112 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.493 AC: 74916 AN: 151970 Hom.: 20158 Cov.: 32 AF XY: 0.496 AC XY: 36813 AN XY: 74266

African (AFR) AF: 0.715 AC: 29655 AN: 41464

American (AMR) AF: 0.528 AC: 8041 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3136 AN: 5164

South Asian (SAS) AF: 0.510 AC: 2458 AN: 4820

European-Finnish (FIN) AF: 0.377 AC: 3985 AN: 10560

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

European-Non Finnish (NFE) AF: 0.368 AC: 24986 AN: 67944

Other (OTH) AF: 0.459 AC: 966 AN: 2106

Alfa AF: 0.454 Hom.: 3261

Bravo AF: 0.514

Asia WGS AF: 0.588 AC: 2049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		1.1
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: rs649610; hg19: chr18-39572258;