rs4121817

Variant names:

• chr18-42009024-G-A
• rs4121817
• NM_002647.4:c.1171-4418G>A

Variant summary

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

The NM_002647.4(PIK3C3):​c.1171-4418G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,000 control chromosomes in the GnomAD database, including 2,109 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 0.16 (2109 hom., cov: 32)
• Consequence: PIK3C3 NM_002647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 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.1171-4418G>A		intron	N/A	NP_002638.2
	PIK3C3	NM_001308020.2		c.982-4418G>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.1171-4418G>A		intron	N/A	ENSP00000262039.3	Q8NEB9
	PIK3C3	ENST00000858068.1		c.1171-4418G>A		intron	N/A	ENSP00000528127.1
	PIK3C3	ENST00000858070.1		c.1171-4418G>A		intron	N/A	ENSP00000528129.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24367 AN: 151884 Hom.: 2106 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.160 AC: 24389 AN: 152000 Hom.: 2109 Cov.: 32 AF XY: 0.162 AC XY: 12029 AN XY: 74286

African (AFR) AF: 0.222 AC: 9215 AN: 41458

American (AMR) AF: 0.152 AC: 2315 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1491 AN: 5152

South Asian (SAS) AF: 0.112 AC: 540 AN: 4824

European-Finnish (FIN) AF: 0.166 AC: 1751 AN: 10580

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8296 AN: 67926

Other (OTH) AF: 0.150 AC: 316 AN: 2108

Alfa AF: 0.161 Hom.: 267

Bravo AF: 0.163

Asia WGS AF: 0.218 AC: 759 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		0.77
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: rs4121817; hg19: chr18-39588988;