rs687528

Variant names:

• chr10-96673848-G-C
• rs687528
• NM_152309.3:c.431-16914C>G

Variant summary

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

The NM_152309.3(PIK3AP1):​c.431-16914C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,042 control chromosomes in the GnomAD database, including 27,810 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 0.58 (27810 hom., cov: 32)
• Consequence: PIK3AP1 NM_152309.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152309.3. 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
	PIK3AP1	NM_152309.3	MANE Select	c.431-16914C>G		intron	N/A	NP_689522.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3AP1	ENST00000339364.10	TSL:1 MANE Select	c.431-16914C>G		intron	N/A	ENSP00000339826.5
	PIK3AP1	ENST00000468783.1	TSL:5	n.77-16914C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87466 AN: 151924 Hom.: 27755 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.663

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.576 AC: 87579 AN: 152042 Hom.: 27810 Cov.: 32 AF XY: 0.571 AC XY: 42410 AN XY: 74320

African (AFR) AF: 0.861 AC: 35734 AN: 41502

American (AMR) AF: 0.569 AC: 8699 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1901 AN: 3472

East Asian (EAS) AF: 0.560 AC: 2890 AN: 5162

South Asian (SAS) AF: 0.534 AC: 2567 AN: 4810

European-Finnish (FIN) AF: 0.384 AC: 4060 AN: 10562

Middle Eastern (MID) AF: 0.669 AC: 194 AN: 290

European-Non Finnish (NFE) AF: 0.440 AC: 29900 AN: 67942

Other (OTH) AF: 0.579 AC: 1221 AN: 2110

Alfa AF: 0.497 Hom.: 2590

Bravo AF: 0.606

Asia WGS AF: 0.597 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.38
PhyloP100		-0.090
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: rs687528; hg19: chr10-98433605;