rs526219

Variant names:

• chr10-96691349-C-T
• rs526219
• NM_152309.3:c.430+18218G>A

Variant summary

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

The NM_152309.3(PIK3AP1):​c.430+18218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,046 control chromosomes in the GnomAD database, including 26,331 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 0.57 (26331 hom., cov: 32)
• Consequence: PIK3AP1 NM_152309.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

Genes affected

PIK3AP1 (HGNC:30034): (phosphoinositide-3-kinase adaptor protein 1) Predicted to enable phosphatidylinositol 3-kinase regulatory subunit binding activity and signaling receptor binding activity. Predicted to be involved in regulation of inflammatory response; regulation of signal transduction; and toll-like receptor signaling pathway. Predicted to be located in cytoplasm and membrane. Predicted to be active in cytosol. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3AP1	NM_152309.3	c.430+18218G>A		intron_variant	Intron 2 of 16	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2	c.430+18218G>A		intron_variant	Intron 2 of 15		XP_011537550.1
PIK3AP1	XM_005269499.2	c.-105+9454G>A		intron_variant	Intron 1 of 15		XP_005269556.1
PIK3AP1	XM_047424566.1	c.-105+18218G>A		intron_variant	Intron 3 of 17		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10	c.430+18218G>A		intron_variant	Intron 2 of 16	1	NM_152309.3	ENSP00000339826.5
PIK3AP1	ENST00000468783.1	n.76+9454G>A		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86606 AN: 151928 Hom.: 26290 Cov.: 32

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.570 AC: 86704 AN: 152046 Hom.: 26331 Cov.: 32 AF XY: 0.568 AC XY: 42197 AN XY: 74328

African (AFR) AF: 0.796 AC: 33020 AN: 41492

American (AMR) AF: 0.559 AC: 8539 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1999 AN: 3470

East Asian (EAS) AF: 0.564 AC: 2913 AN: 5164

South Asian (SAS) AF: 0.576 AC: 2774 AN: 4818

European-Finnish (FIN) AF: 0.403 AC: 4255 AN: 10562

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31325 AN: 67950

Other (OTH) AF: 0.600 AC: 1267 AN: 2112

Alfa AF: 0.509 Hom.: 9851

Bravo AF: 0.594

Asia WGS AF: 0.594 AC: 2068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.48
PhyloP100		1.2
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: rs526219; hg19: chr10-98451106; COSMIC: COSV59530858;